Neutrophil diversity and function in health and disease

0
Neutrophil diversity and function in health and disease
  • Mestas, J. & Hughes, C. C. W. Of mice and not men: differences between mouse and human immunology. J. Immunol. Baltim. Md 1950 172, 2731–2738 (2004).

    CAS 

    Google Scholar 

  • Ng, L. G., Ostuni, R. & Hidalgo, A. Heterogeneity of neutrophils. Nat. Rev. Immunol. 19, 255–265 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Tak, T., Tesselaar, K., Pillay, J., Borghans, J. A. M. & Koenderman, L. What’s your age again? Determination of human neutrophil half-lives revisited. J. Leukoc. Biol. 94, 595–601 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Borregaard, N. Neutrophils, from marrow to microbes. Immunity 33, 657–670 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Carnevale, S. et al. Neutrophil diversity in inflammation and cancer. Front. Immunol. 14, 1180810 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lahoz-Beneytez, J. et al. Human neutrophil kinetics: modeling of stable isotope labeling data supports short blood neutrophil half-lives. Blood 127, 3431–3438 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ng, M. S. F. et al. Deterministic reprogramming of neutrophils within tumors. Science 383, eadf6493 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Nathan, C. Neutrophils and immunity: challenges and opportunities. Nat. Rev. Immunol. 6, 173–182 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ley, K., Laudanna, C., Cybulsky, M. I. & Nourshargh, S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat. Rev. Immunol. 7, 678–689 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sadik, C. D., Kim, N. D. & Luster, A. D. Neutrophils cascading their way to inflammation. Trends Immunol. 32, 452–460 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Soehnlein, O. & Lindbom, L. Phagocyte partnership during the onset and resolution of inflammation. Nat. Rev. Immunol. 10, 427–439 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ballesteros, I. et al. Co-option of neutrophil fates by tissue environments. Cell 183, 1282–1297.e18 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Dotta, L., Tassone, L. & Badolato, R. Clinical and genetic features of Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM) syndrome. Curr. Mol. Med. 11, 317–325 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zeidler, C., Germeshausen, M., Klein, C. & Welte, K. Clinical implications of ELA2-, HAX1-, and G-CSF-receptor (CSF3R) mutations in severe congenital neutropenia. Br. J. Haematol. 144, 459–467 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Silvestre-Roig, C., Hidalgo, A. & Soehnlein, O. Neutrophil heterogeneity: implications for homeostasis and pathogenesis. Blood 127, 2173–2181 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Liew, P. X. & Kubes, P. The neutrophil’s role during health and disease. Physiol. Rev. 99, 1223–1248 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Futosi, K., Fodor, S. & Mócsai, A. Neutrophil cell surface receptors and their intracellular signal transduction pathways. Int. Immunopharmacol. 17, 638–650 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, K. L., Chen, S. N., Li, L., Huo, H. J. & Nie, P. Functional characterization of four TIR domain-containing adaptors, MyD88, TRIF, MAL, and SARM in mandarin fish Siniperca chuatsi. Dev. Comp. Immunol. 122, 104110 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Fetz, A. E., Radic, M. Z. & Bowlin, G. L. Human neutrophil FcγRIIIb regulates neutrophil extracellular trap release in response to electrospun polydioxanone biomaterials. Acta Biomater. 130, 281–290 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Syrovatkina, V., Alegre, K. O., Dey, R. & Huang, X.-Y. Regulation, signaling, and physiological functions of G-proteins. J. Mol. Biol. 428, 3850–3868 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Futosi, K. & Mócsai, A. Tyrosine kinase signaling pathways in neutrophils. Immunol. Rev. 273, 121–139 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bouti, P. et al. β2 integrin signaling cascade in neutrophils: more than a single function. Front. Immunol. 11, 619925 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Rajarathnam, K., Schnoor, M., Richardson, R. M. & Rajagopal, S. How do chemokines navigate neutrophils to the target site: dissecting the structural mechanisms and signaling pathways. Cell. Signal. 54, 69–80 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • van Leeuwenhoek, A. Microscopical Observations from Mr. Leeuwenhoek, about Blood, Milk, Bones, the Brain, Spitle, Cuticula, Sweat, Fatt, Teares: Communicated in Two Letters to the Publisher … (Royal Society, 1674).

  • Hajdu, S. I. A note from history: the discovery of blood cells. Ann. Clin. Lab. Sci. 33, 237–238 (2003).

    PubMed 

    Google Scholar 

  • Kay, A. B. The early history of the eosinophil. Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol. 45, 575–582 (2015).

    Article 
    CAS 

    Google Scholar 

  • Kay, A. B. Paul Ehrlich and the early history of granulocytes. Microbiol. Spectr. 4, 10–1128 (2016).

    Article 

    Google Scholar 

  • Drews, J. Paul Ehrlich: magister mundi. Nat. Rev. Drug Discov. 3, 797–801 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Di Donato, R., Bonecchi, R. & Albano, F. Canonical and atypical chemokine receptors in the neutrophil life cycle. Cytokine 169, 156297 (2023).

    Article 
    PubMed 

    Google Scholar 

  • Metzemaekers, M., Gouwy, M. & Proost, P. Neutrophil chemoattractant receptors in health and disease: double-edged swords. Cell. Mol. Immunol. 17, 433–450 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Petri, B. & Sanz, M.-J. Neutrophil chemotaxis. Cell Tissue Res. 371, 425–436 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Eash, K. J., Means, J. M., White, D. W. & Link, D. C. CXCR4 is a key regulator of neutrophil release from the bone marrow under basal and stress granulopoiesis conditions. Blood 113, 4711–4719 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Subramanian, B. C., Majumdar, R. & Parent, C. A. The role of the LTB4-BLT1 axis in chemotactic gradient sensing and directed leukocyte migration. Semin. Immunol. 33, 16–29 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mehta, H. M. & Corey, S. J. G-CSF, the guardian of granulopoiesis. Semin. Immunol. 54, 101515 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Welte, K. et al. Purification and biochemical characterization of human pluripotent hematopoietic colony-stimulating factor. Proc. Natl. Acad. Sci. USA 82, 1526–1530 (1985).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hill, C. P., Osslund, T. D. & Eisenberg, D. The structure of granulocyte-colony-stimulating factor and its relationship to other growth factors. Proc. Natl. Acad. Sci. USA 90, 5167–5171 (1993).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Nagata, S. et al. Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nature 319, 415–418 (1986).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Souza, L. M. et al. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science 232, 61–65 (1986).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Metcalf, D. The colony-stimulating factors and cancer. Cancer Immunol. Res. 1, 351–356 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gabrilove, J. L. et al. Effect of granulocyte colony-stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional-cell carcinoma of the urothelium. N. Engl. J. Med. 318, 1414–1422 (1988).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bronchud, M. H. et al. Phase I/II study of recombinant human granulocyte colony-stimulating factor in patients receiving intensive chemotherapy for small cell lung cancer. Br. J. Cancer 56, 809–813 (1987).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Özcan, A. & Boyman, O. Mechanisms regulating neutrophil responses in immunity, allergy, and autoimmunity. Allergy 77, 3567–3583 (2022).

    Article 
    PubMed 

    Google Scholar 

  • Kolaczkowska, E. & Kubes, P. Neutrophil recruitment and function in health and inflammation. Nat. Rev. Immunol. 13, 159–175 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Springer, T. A. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76, 301–314 (1994).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ivetic, A. A head-to-tail view of L-selectin and its impact on neutrophil behaviour. Cell Tissue Res. 371, 437–453 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Calderwood, D. A., Shattil, S. J. & Ginsberg, M. H. Integrins and actin filaments: reciprocal regulation of cell adhesion and signaling. J. Biol. Chem. 275, 22607–22610 (2000).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Nourshargh, S., Renshaw, S. A. & Imhof, B. A. Reverse migration of neutrophils: where, when, how, and why? Trends Immunol. 37, 273–286 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Maas, S. L., Soehnlein, O. & Viola, J. R. Organ-specific mechanisms of transendothelial neutrophil migration in the lung, liver, kidney, and aorta. Front. Immunol. 9, 2739 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Margraf, A., Ley, K. & Zarbock, A. Neutrophil recruitment: from model systems to tissue-specific patterns. Trends Immunol. 40, 613–634 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hampton, M. B. & Dickerhof, N. Inside the phagosome: a bacterial perspective. Immunol. Rev. 314, 197–209 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Cohn, Z. A. & Hirsch, J. G. The influence of phagocytosis on the intracellular distribution of granule-associated components of polymorphonuclear leucocytes. J. Exp. Med. 112, 1015–1022 (1960).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Levin, R., Grinstein, S. & Canton, J. The life cycle of phagosomes: formation, maturation, and resolution. Immunol. Rev. 273, 156–179 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Naish, E. et al. The formation and function of the neutrophil phagosome. Immunol. Rev. 314, 158–180 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Nordenfelt, P. & Tapper, H. Phagosome dynamics during phagocytosis by neutrophils. J. Leukoc. Biol. 90, 271–284 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Krige, D. et al. CHR-2797: an antiproliferative aminopeptidase inhibitor that leads to amino acid deprivation in human leukemic cells. Cancer Res. 68, 6669–6679 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Day, R. B. & Link, D. C. Regulation of neutrophil trafficking from the bone marrow. Cell. Mol. Life Sci. CMLS 69, 1415–1423 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Tu, H. et al. Dying to defend: neutrophil death pathways and their implications in immunity. Adv. Sci. Weinh. Baden.-Wurtt. Ger. 11, e2306457 (2024).

    Google Scholar 

  • Kerr, J. F., Wyllie, A. H. & Currie, A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26, 239–257 (1972).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cookson, B. T. & Brennan, M. A. Pro-inflammatory programmed cell death. Trends Microbiol. 9, 113–114 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Dixon, S. J. et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. cell 149, 1060–1072 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Phillipson, M. & Kubes, P. The healing power of neutrophils. Trends Immunol. 40, 635–647 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Brinkmann, V. et al. Neutrophil extracellular traps kill bacteria. Science 303, 1532–1535 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Filippi, M.-D. Neutrophil transendothelial migration: updates and new perspectives. Blood 133, 2149–2158 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mathias, J. R. et al. Resolution of inflammation by retrograde chemotaxis of neutrophils in transgenic zebrafish. J. Leukoc. Biol. 80, 1281–1288 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zhao, Y., Rahmy, S., Liu, Z., Zhang, C. & Lu, X. Rational targeting of immunosuppressive neutrophils in cancer. Pharmacol. Ther. 212, 107556 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Grecian, R., Whyte, M. K. B. & Walmsley, S. R. The role of neutrophils in cancer. Br. Med. Bull. 128, 5–14 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Fridlender, Z. G. et al. Polarization of tumor-associated neutrophil phenotype by TGF-beta: ‘N1’ versus ‘N2’ TAN. Cancer Cell 16, 183–194 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Andzinski, L. et al. Type I IFNs induce anti-tumor polarization of tumor associated neutrophils in mice and human. Int. J. Cancer 138, 1982–1993 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zhou, J., Nefedova, Y., Lei, A. & Gabrilovich, D. Neutrophils and PMN-MDSC: their biological role and interaction with stromal cells. Semin. Immunol. 35, 19–28 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Condamine, T. et al. Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients. Sci. Immunol. 1, aaf8943 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sagiv, J. Y. et al. Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer. Cell Rep. 10, 562–573 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Mantovani, A., Cassatella, M. A., Costantini, C. & Jaillon, S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat. Rev. Immunol. 11, 519–531 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kolaczkowska, E. Immunosuppressive lung neutrophils. Blood 140, 802–803 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Volberding, P. J. et al. Suppressive neutrophils require PIM1 for metabolic fitness and survival during chronic viral infection. Cell Rep. 35, 109160 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Huang, X. et al. Neutrophils in Cancer immunotherapy: friends or foes? Mol. Cancer 23, 107 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Qi, X. et al. Identification and characterization of neutrophil heterogeneity in sepsis. Crit. Care Lond. Engl. 25, 50 (2021).

    Article 

    Google Scholar 

  • Pillay, J. et al. A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1. J. Clin. Invest. 122, 327–336 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Demaret, J. et al. Marked alterations of neutrophil functions during sepsis-induced immunosuppression. J. Leukoc. Biol. 98, 1081–1090 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bae, G. H. et al. Unique characteristics of lung-resident neutrophils are maintained by PGE2/PKA/Tgm2-mediated signaling. Blood 140, 889–899 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bjerregaard, M. D., Jurlander, J., Klausen, P., Borregaard, N. & Cowland, J. B. The in vivo profile of transcription factors during neutrophil differentiation in human bone marrow. Blood 101, 4322–4332 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Qu, J., Jin, J., Zhang, M. & Ng, L. G. Neutrophil diversity and plasticity: implications for organ transplantation. Cell. Mol. Immunol. 20, 993–1001 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Evrard, M. et al. Developmental analysis of bone marrow neutrophils reveals populations specialized in expansion, trafficking, and effector functions. Immunity 48, 364–379.e8 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kwok, I. et al. Combinatorial single-cell analyses of granulocyte-monocyte progenitor heterogeneity reveals an early uni-potent neutrophil progenitor. Immunity 53, 303–318.e5 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Calzetti, F. et al. CD66b-CD64dimCD115- cells in the human bone marrow represent neutrophil-committed progenitors. Nat. Immunol. 23, 679–691 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Khoyratty, T. E. et al. Distinct transcription factor networks control neutrophil-driven inflammation. Nat. Immunol. 22, 1093–1106 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Silvestre-Roig, C., Kalafati, L. & Chavakis, T. Neutrophils are shaped by the tumor microenvironment: novel possibilities for targeting neutrophils in cancer. Signal Transduct. Target. Ther. 9, 77 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kraus, R. F. & Gruber, M. A. Neutrophils-from bone marrow to first-line defense of the innate immune system. Front. Immunol. 12, 767175 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Laurenti, E. & Göttgens, B. From haematopoietic stem cells to complex differentiation landscapes. Nature 553, 418–426 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chavakis, T., Wielockx, B. & Hajishengallis, G. Inflammatory modulation of hematopoiesis: linking trained immunity and clonal hematopoiesis with chronic disorders. Annu. Rev. Physiol. 84, 183–207 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hidalgo, A., Chilvers, E. R., Summers, C. & Koenderman, L. The neutrophil life cycle. Trends Immunol. 40, 584–597 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Borregaard, N. & Cowland, J. B. Granules of the human neutrophilic polymorphonuclear leukocyte. Blood 89, 3503–3521 (1997).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zhu, Y. P. et al. Identification of an early unipotent neutrophil progenitor with pro-tumoral activity in mouse and human bone marrow. Cell Rep. 24, 2329–2341.e8 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Summers, C. et al. Neutrophil kinetics in health and disease. Trends Immunol. 31, 318–324 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rademakers, T. et al. Hematopoietic stem and progenitor cells use podosomes to transcellularly cross the bone marrow endothelium. Haematologica 105, 2746–2756 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Burdon, P. C. E., Martin, C. & Rankin, S. M. Migration across the sinusoidal endothelium regulates neutrophil mobilization in response to ELR + CXC chemokines. Br. J. Haematol. 142, 100–108 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Fossiez, F. et al. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J. Exp. Med. 183, 2593–2603 (1996).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ye, P. et al. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J. Exp. Med. 194, 519–527 (2001).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Panopoulos, A. D. & Watowich, S. S. Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and ‘emergency’ hematopoiesis. Cytokine 42, 277–288 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhu, Q.-S. et al. G-CSF induced reactive oxygen species involves Lyn-PI3-kinase-Akt and contributes to myeloid cell growth. Blood 107, 1847–1856 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • de Koning, J. P. et al. The membrane-distal cytoplasmic region of human granulocyte colony-stimulating factor receptor is required for STAT3 but not STAT1 homodimer formation. Blood 87, 1335–1342 (1996).

    Article 
    PubMed 

    Google Scholar 

  • Nicholson, S. E., Novak, U., Ziegler, S. F. & Layton, J. E. Distinct regions of the granulocyte colony-stimulating factor receptor are required for tyrosine phosphorylation of the signaling molecules JAK2, Stat3, and p42, p44MAPK. Blood 86, 3698–3704 (1995).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • McLemore, M. L. et al. STAT-3 activation is required for normal G-CSF-dependent proliferation and granulocytic differentiation. Immunity 14, 193–204 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kamezaki, K. et al. Roles of Stat3 and ERK in G-CSF signaling. Stem Cells Dayt. Ohio 23, 252–263 (2005).

    Article 
    CAS 

    Google Scholar 

  • van Raam, B. J., Drewniak, A., Groenewold, V., van den Berg, T. K. & Kuijpers, T. W. Granulocyte colony-stimulating factor delays neutrophil apoptosis by inhibition of calpains upstream of caspase-3. Blood 112, 2046–2054 (2008).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Raffaghello, L. et al. Human mesenchymal stem cells inhibit neutrophil apoptosis: a model for neutrophil preservation in the bone marrow niche. Stem Cells Dayt. Ohio 26, 151–162 (2008).

    Article 
    CAS 

    Google Scholar 

  • Kim, H. K., De La Luz Sierra, M., Williams, C. K., Gulino, A. V. & Tosato, G. G-CSF down-regulation of CXCR4 expression identified as a mechanism for mobilization of myeloid cells. Blood 108, 812–820 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Eash, K. J., Greenbaum, A. M., Gopalan, P. K. & Link, D. C. CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow. J. Clin. Invest. 120, 2423–2431 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Osaka, M. et al. Critical role of the C5a-activated neutrophils in high-fat diet-induced vascular inflammation. Sci. Rep. 6, 21391 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Patin, E. C., Thompson, A. & Orr, S. J. Pattern recognition receptors in fungal immunity. Semin. Cell Dev. Biol. 89, 24–33 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Santoni, G. et al. Danger- and pathogen-associated molecular patterns recognition by pattern-recognition receptors and ion channels of the transient receptor potential family triggers the inflammasome activation in immune cells and sensory neurons. J. Neuroinflammation 12, 21 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kunkel, E. J., Jung, U. & Ley, K. TNF-alpha induces selectin-mediated leukocyte rolling in mouse cremaster muscle arterioles. Am. J. Physiol. 272, H1391–1400 (1997).

    CAS 
    PubMed 

    Google Scholar 

  • Zarbock, A., Ley, K., McEver, R. P. & Hidalgo, A. Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow. Blood 118, 6743–6751 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Eriksson, E. E., Xie, X., Werr, J., Thoren, P. & Lindbom, L. Importance of primary capture and L-selectin-dependent secondary capture in leukocyte accumulation in inflammation and atherosclerosis in vivo. J. Exp. Med. 194, 205–218 (2001).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kunkel, E. J. & Ley, K. Distinct phenotype of E-selectin-deficient mice. E-selectin is required for slow leukocyte rolling in vivo. Circ. Res. 79, 1196–1204 (1996).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Mayadas, T. N., Johnson, R. C., Rayburn, H., Hynes, R. O. & Wagner, D. D. Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice. Cell 74, 541–554 (1993).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kuwano, Y., Spelten, O., Zhang, H., Ley, K. & Zarbock, A. Rolling on E- or P-selectin induces the extended but not high-affinity conformation of LFA-1 in neutrophils. Blood 116, 617–624 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Snapp, K. R., Heitzig, C. E. & Kansas, G. S. Attachment of the PSGL-1 cytoplasmic domain to the actin cytoskeleton is essential for leukocyte rolling on P-selectin. Blood 99, 4494–4502 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ramachandran, V., Williams, M., Yago, T., Schmidtke, D. W. & McEver, R. P. Dynamic alterations of membrane tethers stabilize leukocyte rolling on P-selectin. Proc. Natl. Acad. Sci. USA 101, 13519–13524 (2004).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Khismatullin, D. B. & Truskey, G. A. Leukocyte rolling on P-selectin: a three-dimensional numerical study of the effect of cytoplasmic viscosity. Biophys. J. 102, 1757–1766 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sundd, P. et al. Slings’ enable neutrophil rolling at high shear. Nature 488, 399–403 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhu, J. et al. Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces. Mol. Cell 32, 849–861 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Nishida, N. et al. Activation of leukocyte beta2 integrins by conversion from bent to extended conformations. Immunity 25, 583–594 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sun, Z., Costell, M. & Fässler, R. Integrin activation by talin, kindlin and mechanical forces. Nat. Cell Biol. 21, 25–31 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Moser, M. et al. Kindlin-3 is required for beta2 integrin-mediated leukocyte adhesion to endothelial cells. Nat. Med. 15, 300–305 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Phillipson, M. et al. Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade. J. Exp. Med. 203, 2569–2575 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • McDonald, B. et al. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science 330, 362–366 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Margraf, A. et al. ArhGAP15, a RacGAP, acts as a temporal signaling regulator of Mac-1 affinity in sterile inflammation. J. Immunol. Baltim. Md 1950 205, 1365–1375 (2020).

    CAS 

    Google Scholar 

  • Yolland, L. et al. Persistent and polarized global actin flow is essential for directionality during cell migration. Nat. Cell Biol. 21, 1370–1381 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hepper, I. et al. The mammalian actin-binding protein 1 is critical for spreading and intraluminal crawling of neutrophils under flow conditions. J. Immunol. Baltim. Md 1950 188, 4590–4601 (2012).

    CAS 

    Google Scholar 

  • Phillipson, M. et al. Vav1 is essential for mechanotactic crawling and migration of neutrophils out of the inflamed microvasculature. J. Immunol. Baltim. Md 1950 182, 6870–6878 (2009).

    CAS 

    Google Scholar 

  • Barreiro, O. et al. Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes. J. Cell Biol. 157, 1233–1245 (2002).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Carman, C. V. & Springer, T. A. A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them. J. Cell Biol. 167, 377–388 (2004).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Petri, B. et al. Endothelial LSP1 is involved in endothelial dome formation, minimizing vascular permeability changes during neutrophil transmigration in vivo. Blood 117, 942–952 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kolaczkowska, E. et al. Neutrophil elastase activity compensates for a genetic lack of matrix metalloproteinase-9 (MMP-9) in leukocyte infiltration in a model of experimental peritonitis. J. Leukoc. Biol. 85, 374–381 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Pieper, C., Pieloch, P. & Galla, H.-J. Pericytes support neutrophil transmigration via interleukin-8 across a porcine co-culture model of the blood-brain barrier. Brain Res. 1524, 1–11 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Pellowe, A. S. et al. Endothelial cell-secreted MIF reduces pericyte contractility and enhances neutrophil extravasation. FASEB J. Publ. Fed. Am. Soc. Exp. Biol. 33, 2171–2186 (2019).

    CAS 

    Google Scholar 

  • Renkawitz, J. et al. Nuclear positioning facilitates amoeboid migration along the path of least resistance. Nature 568, 546–550 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lerchenberger, M. et al. Matrix metalloproteinases modulate ameboid-like migration of neutrophils through inflamed interstitial tissue. Blood 122, 770–780 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sadik, C. D. & Luster, A. D. Lipid-cytokine-chemokine cascades orchestrate leukocyte recruitment in inflammation. J. Leukoc. Biol. 91, 207–215 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Pollard, T. D. & Borisy, G. G. Cellular motility driven by assembly and disassembly of actin filaments. Cell 112, 453–465 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Van Haastert, P. J. M. & Devreotes, P. N. Chemotaxis: signalling the way forward. Nat. Rev. Mol. Cell Biol. 5, 626–634 (2004).

    Article 
    PubMed 

    Google Scholar 

  • Coates, T. D., Watts, R. G., Hartman, R. & Howard, T. H. Relationship of F-actin distribution to development of polar shape in human polymorphonuclear neutrophils. J. Cell Biol. 117, 765–774 (1992).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Daly, C. A., Hall, E. T. & Ogden, S. K. Regulatory mechanisms of cytoneme-based morphogen transport. Cell. Mol. Life Sci. CMLS 79, 119 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Devreotes, P. & Janetopoulos, C. Eukaryotic chemotaxis: distinctions between directional sensing and polarization. J. Biol. Chem. 278, 20445–20448 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Michael, M. & Vermeren, S. A neutrophil-centric view of chemotaxis. Essays Biochem 63, 607–618 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Levi, S., Polyakov, M. V. & Egelhoff, T. T. Myosin II dynamics in Dictyostelium: determinants for filament assembly and translocation to the cell cortex during chemoattractant responses. Cell Motil. Cytoskeleton 53, 177–188 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Flannagan, R. S., Jaumouillé, V. & Grinstein, S. The cell biology of phagocytosis. Annu. Rev. Pathol. 7, 61–98 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Nobes, C. D. & Hall, A. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81, 53–62 (1995).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Mócsai, A. Diverse novel functions of neutrophils in immunity, inflammation, and beyond. J. Exp. Med. 210, 1283–1299 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rørvig, S., Østergaard, O., Heegaard, N. H. H. & Borregaard, N. Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane: correlation with transcriptome profiling of neutrophil precursors. J. Leukoc. Biol. 94, 711–721 (2013).

    Article 
    PubMed 

    Google Scholar 

  • Flannagan, R. S., Cosío, G. & Grinstein, S. Antimicrobial mechanisms of phagocytes and bacterial evasion strategies. Nat. Rev. Microbiol. 7, 355–366 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Dandekar, S. N. et al. Actin dynamics rapidly reset chemoattractant receptor sensitivity following adaptation in neutrophils. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 368, 20130008 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Siraki, A. G. The many roles of myeloperoxidase: from inflammation and immunity to biomarkers, drug metabolism and drug discovery. Redox Biol. 46, 102109 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Soehnlein, O., Steffens, S., Hidalgo, A. & Weber, C. Neutrophils as protagonists and targets in chronic inflammation. Nat. Rev. Immunol. 17, 248–261 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Lawrence, S. M., Corriden, R. & Nizet, V. How neutrophils meet their end. Trends Immunol. 41, 531–544 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Geering, B. & Simon, H.-U. Peculiarities of cell death mechanisms in neutrophils. Cell Death Differ. 18, 1457–1469 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kobayashi, S. D., DeLeo, F. R. & Quinn, M. T. Microbes and the fate of neutrophils. Immunol. Rev. 314, 210–228 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Tait, S. W. G. & Green, D. R. Mitochondria and cell death: outer membrane permeabilization and beyond. Nat. Rev. Mol. Cell Biol. 11, 621–632 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ranjan, K. & Pathak, C. Cellular dynamics of Fas-associated death domain in the regulation of cancer and inflammation. Int. J. Mol. Sci. 25, 3228 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Voll, R. E. et al. Immunosuppressive effects of apoptotic cells. Nature 390, 350–351 (1997).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Morioka, S., Maueröder, C. & Ravichandran, K. S. Living on the Edge: efferocytosis at the interface of homeostasis and pathology. Immunity 50, 1149–1162 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bäck, M., Yurdagul, A., Tabas, I., Öörni, K. & Kovanen, P. T. Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities. Nat. Rev. Cardiol. 16, 389–406 (2019).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Bagaitkar, J. et al. NADPH oxidase activation regulates apoptotic neutrophil clearance by murine macrophages. Blood 131, 2367–2378 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kobayashi, S. D. et al. Gene expression profiling provides insight into the pathophysiology of chronic granulomatous disease. J. Immunol. Baltim. Md 1950 172, 636–643 (2004).

    CAS 

    Google Scholar 

  • Wang, X., He, Z., Liu, H., Yousefi, S. & Simon, H.-U. Neutrophil necroptosis is triggered by ligation of adhesion molecules following GM-CSF priming. J. Immunol. Baltim. Md 1950 197, 4090–4100 (2016).

    CAS 

    Google Scholar 

  • Mihalache, C. C. et al. Inflammation-associated autophagy-related programmed necrotic death of human neutrophils characterized by organelle fusion events. J. Immunol. Baltim. Md 1950 186, 6532–6542 (2011).

    CAS 

    Google Scholar 

  • Wicki, S. et al. Loss of XIAP facilitates switch to TNFα-induced necroptosis in mouse neutrophils. Cell Death Dis. 7, e2422 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • He, S. et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 137, 1100–1111 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sun, L. et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell 148, 213–227 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Greenlee-Wacker, M. C. et al. Phagocytosis of Staphylococcus aureus by human neutrophils prevents macrophage efferocytosis and induces programmed necrosis. J. Immunol. Baltim. Md 1950 192, 4709–4717 (2014).

    CAS 

    Google Scholar 

  • van Zandbergen, G. et al. Chlamydia pneumoniae multiply in neutrophil granulocytes and delay their spontaneous apoptosis. J. Immunol. Baltim. Md 1950 172, 1768–1776 (2004).

    Google Scholar 

  • Jondle, C. N., Gupta, K., Mishra, B. B. & Sharma, J. Klebsiella pneumoniae infection of murine neutrophils impairs their efferocytic clearance by modulating cell death machinery. PLoS Pathog. 14, e1007338 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Thieblemont, N., Witko-Sarsat, V. & Ariel, A. Regulation of macrophage activation by proteins expressed on apoptotic neutrophils: Subversion towards autoimmunity by proteinase 3. Eur. J. Clin. Invest. 48, e12990 (2018).

    Article 
    PubMed 

    Google Scholar 

  • Shi, J. et al. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature 514, 187–192 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Van Opdenbosch, N. & Lamkanfi, M. Caspases in cell death, inflammation, and disease. Immunity 50, 1352–1364 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Shi, J. et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526, 660–665 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Stockwell, B. R. et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171, 273–285 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sun, S., Shen, J., Jiang, J., Wang, F. & Min, J. Targeting ferroptosis opens new avenues for the development of novel therapeutics. Signal Transduct. Target. Ther. 8, 372 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Veglia, F. et al. Fatty acid transport protein 2 reprograms neutrophils in cancer. Nature 569, 73–78 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kim, R. et al. Ferroptosis of tumour neutrophils causes immune suppression in cancer. Nature 612, 338–346 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Baz, A. A. et al. Neutrophil extracellular traps in bacterial infections and evasion strategies. Front. Immunol. 15, 1357967 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yipp, B. G. & Kubes, P. NETosis: how vital is it? Blood 122, 2784–2794 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Papayannopoulos, V., Metzler, K. D., Hakkim, A. & Zychlinsky, A. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J. Cell Biol. 191, 677–691 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sollberger, G. et al. Gasdermin D plays a vital role in the generation of neutrophil extracellular traps. Sci. Immunol. 3, eaar6689 (2018).

    Article 
    PubMed 

    Google Scholar 

  • Leshner, M. et al. PAD4 mediated histone hypercitrullination induces heterochromatin decondensation and chromatin unfolding to form neutrophil extracellular trap-like structures. Front. Immunol. 3, 307 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jorch, S. K. & Kubes, P. An emerging role for neutrophil extracellular traps in noninfectious disease. Nat. Med. 23, 279–287 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Eustache, J. H. et al. Casting a wide net on surgery: the central role of neutrophil extracellular traps. Ann. Surg. 272, 277–283 (2020).

    Article 
    PubMed 

    Google Scholar 

  • Schoen, J. et al. Neutrophils’ extracellular trap mechanisms: from physiology to pathology. Int. J. Mol. Sci. 23, 12855 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ronchetti, L. et al. Neutrophil extracellular traps in cancer: not only catching microbes. J. Exp. Clin. Cancer Res. 40, 231 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • James, P., Kaushal, D. & Beaumont Wilson, R. NETosis in surgery: pathophysiology, prevention, and treatment. Ann. Surg. 279, 765–780 (2024).

    PubMed 

    Google Scholar 

  • Wong, S. L. et al. Diabetes primes neutrophils to undergo NETosis, which impairs wound healing. Nat. Med. 21, 815–819 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Liu, D. et al. NLRP3 activation induced by neutrophil extracellular traps sustains inflammatory response in the diabetic wound. Clin. Sci. Lond. Engl. 1979 133, 565–582 (2019).

    CAS 

    Google Scholar 

  • Yang, S. et al. Neutrophil extracellular traps delay diabetic wound healing by inducing endothelial-to-mesenchymal transition via the hippo pathway. Int. J. Biol. Sci. 19, 347–361 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Souza, F. W. & Miao, E. A. Neutrophils only die twice. Sci. Adv. 9, eadm8715 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Elks, P. M. et al. Activation of hypoxia-inducible factor-1α (Hif-1α) delays inflammation resolution by reducing neutrophil apoptosis and reverse migration in a zebrafish inflammation model. Blood 118, 712–722 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Woodfin, A. et al. The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo. Nat. Immunol. 12, 761–769 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hamza, B. et al. Retrotaxis of human neutrophils during mechanical confinement inside microfluidic channels. Integr. Biol. Quant. Biosci. Nano Macro 6, 175–183 (2014).

    CAS 

    Google Scholar 

  • Colom, B. et al. Leukotriene B4-neutrophil elastase axis drives neutrophil reverse transendothelial cell migration in vivo. Immunity 42, 1075–1086 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tharp, W. G. et al. Neutrophil chemorepulsion in defined interleukin-8 gradients in vitro and in vivo. J. Leukoc. Biol. 79, 539–554 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Serhan, C. N., Chiang, N., Dalli, J. & Levy, B. D. Lipid mediators in the resolution of inflammation. Cold Spring Harb. Perspect. Biol. 7, a016311 (2014).

    Article 
    PubMed 

    Google Scholar 

  • Martin, C. et al. Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence. Immunity 19, 583–593 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Casbon, A.-J. et al. Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils. Proc. Natl. Acad. Sci. USA 112, E566–575 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Fisher, D. T., Appenheimer, M. M. & Evans, S. S. The two faces of IL-6 in the tumor microenvironment. Semin. Immunol. 26, 38–47 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Horvath, L. et al. Beyond binary: bridging neutrophil diversity to new therapeutic approaches in NSCLC. Trends Cancer 10, 457–474 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sun, B. et al. Neutrophil suppresses tumor cell proliferation via Fas /Fas ligand pathway mediated cell cycle arrested. Int. J. Biol. Sci. 14, 2103–2113 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gershkovitz, M. et al. TRPM2 mediates neutrophil killing of disseminated tumor cells. Cancer Res. 78, 2680–2690 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sun, H. et al. Formyl peptide enhances cancer immunotherapy by activating antitumoral neutrophils, and T cells. Biomed. Pharmacother. Biomed. Pharmacother. 175, 116670 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Korbecki, J. et al. The effect of hypoxia on the expression of CXC chemokines and CXC chemokine receptors-a review of literature. Int. J. Mol. Sci. 22, 843 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Li, S. et al. Tumor-associated neutrophils induce EMT by IL-17a to promote migration and invasion in gastric cancer cells. J. Exp. Clin. Cancer Res. CR 38, 6 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Fares, J., Fares, M. Y., Khachfe, H. H., Salhab, H. A. & Fares, Y. Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduct. Target. Ther. 5, 28 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cheng, Y. et al. Cancer-associated fibroblasts induce PDL1+ neutrophils through the IL6-STAT3 pathway that foster immune suppression in hepatocellular carcinoma. Cell Death Dis. 9, 422 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kwantwi, L. B. et al. Tumor-associated neutrophils activated by tumor-derived CCL20 (C-C motif chemokine ligand 20) promote T cell immunosuppression via programmed death-ligand 1 (PD-L1) in breast cancer. Bioengineered 12, 6996–7006 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, T.-T. et al. Tumour-activated neutrophils in gastric cancer foster immune suppression and disease progression through GM-CSF-PD-L1 pathway. Gut 66, 1900–1911 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Salmaninejad, A. et al. PD-1/PD-L1 pathway: basic biology and role in cancer immunotherapy. J. Cell. Physiol. 234, 16824–16837 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Filippone, A. et al. PD1/PD-L1 immune checkpoint as a potential target for preventing brain tumor progression. Cancer Immunol. Immunother. CII 71, 2067–2075 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ring, N. G. et al. Anti-SIRPα antibody immunotherapy enhances neutrophil and macrophage antitumor activity. Proc. Natl. Acad. Sci. USA 114, E10578–E10585 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yu, X. et al. Neutrophils in cancer: dual roles through intercellular interactions. Oncogene 43, 1163–1177 (2024).

    CAS 
    PubMed 

    Google Scholar 

  • Yang, S. et al. Targeting neutrophils: mechanism and advances in cancer therapy. Clin. Transl. Med. 14, e1599 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cedervall, J., Zhang, Y. & Olsson, A.-K. Tumor-induced NETosis as a risk factor for metastasis and organ failure. Cancer Res. 76, 4311–4315 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Tohme, S. et al. Neutrophil extracellular traps promote the development and progression of liver metastases after surgical stress. Cancer Res. 76, 1367–1380 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yang, L. et al. DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25. Nature 583, 133–138 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Okamoto, M. et al. Neutrophil extracellular traps promote metastases of colorectal cancers through activation of ERK signaling by releasing neutrophil elastase. Int. J. Mol. Sci. 24, 1118 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Albrengues, J. et al. Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science 361, eaao4227 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, Y., Du, C., Zhang, Y. & Zhu, L. Composition and function of neutrophil extracellular traps. Biomolecules 14, 416 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Teijeira, Á. et al. CXCR1 and CXCR2 chemokine receptor agonists produced by tumors induce neutrophil extracellular traps that interfere with immune cytotoxicity. Immunity 52, 856–871.e8 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zhang, H. et al. Neutrophils extracellular traps inhibition improves PD-1 blockade immunotherapy in colorectal cancer. Cancers 13, 5333 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Salcher, S. et al. High-resolution single-cell atlas reveals diversity and plasticity of tissue-resident neutrophils in non-small cell lung cancer. Cancer Cell 40, 1503–1520.e8 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wigerblad, G. et al. Single-cell analysis reveals the range of transcriptional states of circulating human neutrophils. J. Immunol. Baltim. Md 1950 209, 772–782 (2022).

    CAS 

    Google Scholar 

  • Montaldo, E. et al. Cellular and transcriptional dynamics of human neutrophils at steady state and upon stress. Nat. Immunol. 23, 1470–1483 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dinh, H. Q. et al. Coexpression of CD71 and CD117 identifies an early unipotent neutrophil progenitor population in human bone marrow. Immunity 53, 319–334.e6 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Xue, R. et al. Liver tumour immune microenvironment subtypes and neutrophil heterogeneity. Nature 612, 141–147 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wang, L. et al. Single-cell RNA-seq analysis reveals BHLHE40-driven pro-tumour neutrophils with hyperactivated glycolysis in pancreatic tumour microenvironment. Gut 72, 958–971 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wu, F. et al. Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer. Nat. Commun. 12, 2540 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wu, Y. et al. Neutrophil profiling illuminates anti-tumor antigen-presenting potency. Cell (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mysore, V. et al. FcγR engagement reprograms neutrophils into antigen cross-presenting cells that elicit acquired anti-tumor immunity. Nat. Commun. 12, 4791 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ma, R. et al. Single-cell RNA sequencing reveals immune cell dysfunction in the peripheral blood of patients with highly aggressive gastric cancer. Cell Prolif. 57, e13591 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Atanasova, M. & Whitty, A. Understanding cytokine and growth factor receptor activation mechanisms. Crit. Rev. Biochem. Mol. Biol. 47, 502–530 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Fan, G. H., Yang, W., Wang, X. J., Qian, Q. & Richmond, A. Identification of a motif in the carboxyl terminus of CXCR2 that is involved in adaptin 2 binding and receptor internalization. Biochemistry 40, 791–800 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Villaseca, S. et al. Gαi protein subunit: a step toward understanding its non-canonical mechanisms. Front. Cell Dev. Biol. 10, 941870 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lehmann, D. M., Seneviratne, A. M. P. B. & Smrcka, A. V. Small molecule disruption of G protein beta gamma subunit signaling inhibits neutrophil chemotaxis and inflammation. Mol. Pharmacol. 73, 410–418 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Winer, B. Y. et al. Plasma membrane abundance dictates phagocytic capacity and functional cross-talk in myeloid cells. Sci. Immunol. 9, eadl2388 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lundgren, S. M. et al. Signaling dynamics distinguish high- and low-priority neutrophil chemoattractant receptors. Sci. Signal. 16, eadd1845 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Migeotte, I., Communi, D. & Parmentier, M. Formyl peptide receptors: a promiscuous subfamily of G protein-coupled receptors controlling immune responses. Cytokine Growth Factor Rev. 17, 501–519 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Boulay, F., Naik, N., Giannini, E., Tardif, M. & Brouchon, L. Phagocyte chemoattractant receptors. Ann. N. Y. Acad. Sci. 832, 69–84 (1997).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Lee, H., Whitfeld, P. L. & Mackay, C. R. Receptors for complement C5a. The importance of C5aR and the enigmatic role of C5L2. Immunol. Cell Biol. 86, 153–160 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Nakamura, M. & Shimizu, T. Leukotriene receptors. Chem. Rev. 111, 6231–6298 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Yokomizo, T., Nakamura, M. & Shimizu, T. Leukotriene receptors as potential therapeutic targets. J. Clin. Invest. 128, 2691–2701 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ohnishi, H., Miyahara, N. & Gelfand, E. W. The role of leukotriene B(4) in allergic diseases. Allergol. Int. J. Jpn. Soc. Allergol. 57, 291–298 (2008).

    Article 
    CAS 

    Google Scholar 

  • Lämmermann, T. et al. Neutrophil swarms require LTB4 and integrins at sites of cell death in vivo. Nature 498, 371–375 (2013).

    Article 
    PubMed 

    Google Scholar 

  • Allendorf, D. J. et al. C5a-mediated leukotriene B4-amplified neutrophil chemotaxis is essential in tumor immunotherapy facilitated by anti-tumor monoclonal antibody and beta-glucan. J. Immunol. Baltim. Md 1950 174, 7050–7056 (2005).

    CAS 

    Google Scholar 

  • Yokomizo, T. & Shimizu, T. The leukotriene B4 receptors BLT1 and BLT2 as potential therapeutic targets. Immunol. Rev. 317, 30–41 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wang, N. et al. Structural basis of leukotriene B4 receptor 1 activation. Nat. Commun. 13, 1156 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Brink, C. et al. International Union of Pharmacology XXXVII. Nomenclature for leukotriene and lipoxin receptors. Pharmacol. Rev. 55, 195–227 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Woo, C.-H. et al. Transepithelial migration of neutrophils in response to leukotriene B4 is mediated by a reactive oxygen species-extracellular signal-regulated kinase-linked cascade. J. Immunol. Baltim. Md 1950 170, 6273–6279 (2003).

    CAS 

    Google Scholar 

  • Tarlowe, M. H. et al. Inflammatory chemoreceptor cross-talk suppresses leukotriene B4 receptor 1-mediated neutrophil calcium mobilization and chemotaxis after trauma. J. Immunol. Baltim. Md 1950 171, 2066–2073 (2003).

    CAS 

    Google Scholar 

  • Nishio, M. et al. Control of cell polarity and motility by the PtdIns(3,4,5)P3 phosphatase SHIP1. Nat. Cell Biol. 9, 36–44 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Mondal, S., Subramanian, K. K., Sakai, J., Bajrami, B. & Luo, H. R. Phosphoinositide lipid phosphatase SHIP1 and PTEN coordinate to regulate cell migration and adhesion. Mol. Biol. Cell 23, 1219–1230 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ito, N. et al. Requirement of phosphatidylinositol 3-kinase activation and calcium influx for leukotriene B4-induced enzyme release. J. Biol. Chem. 277, 44898–44904 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ferguson, G. J. et al. PI(3)Kgamma has an important context-dependent role in neutrophil chemokinesis. Nat. Cell Biol. 9, 86–91 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Devreotes, P. & Horwitz, A. R. Signaling networks that regulate cell migration. Cold Spring Harb. Perspect. Biol. 7, a005959 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chen, J., Tang, H., Hay, N., Xu, J. & Ye, R. D. Akt isoforms differentially regulate neutrophil functions. Blood 115, 4237–4246 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sánchez-Galán, E. et al. Leukotriene B4 enhances the activity of nuclear factor-kappaB pathway through BLT1 and BLT2 receptors in atherosclerosis. Cardiovasc. Res. 81, 216–225 (2009).

    Article 
    PubMed 

    Google Scholar 

  • Ichiki, T., Koga, T. & Yokomizo, T. Receptor for advanced glycation end products regulates leukotriene B4 receptor 1 signaling. DNA Cell Biol. 35, 747–750 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ichiki, T. et al. Modulation of leukotriene B4 receptor 1 signaling by receptor for advanced glycation end products (RAGE). FASEB J. Publ. Fed. Am. Soc. Exp. Biol. 30, 1811–1822 (2016).

    CAS 

    Google Scholar 

  • He, R., Chen, Y. & Cai, Q. The role of the LTB4-BLT1 axis in health and disease. Pharmacol. Res. 158, 104857 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Laumonnier, Y., Karsten, C. M. & Köhl, J. Novel insights into the expression pattern of anaphylatoxin receptors in mice and men. Mol. Immunol. 89, 44–58 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Vandendriessche, S., Cambier, S., Proost, P. & Marques, P. E. Complement receptors and their role in leukocyte recruitment and phagocytosis. Front. Cell Dev. Biol. 9, 624025 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Santos-López, J., de la Paz, K., Fernández, F. J. & Vega, M. C. Structural biology of complement receptors. Front. Immunol. 14, 1239146 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Haviland, D. L. et al. Cellular expression of the C5a anaphylatoxin receptor (C5aR): demonstration of C5aR on nonmyeloid cells of the liver and lung. J. Immunol. Baltim. Md 1950 154, 1861–1869 (1995).

    CAS 

    Google Scholar 

  • Schieferdecker, H. L., Schlaf, G., Jungermann, K. & Götze, O. Functions of anaphylatoxin C5a in rat liver: direct and indirect actions on nonparenchymal and parenchymal cells. Int. Immunopharmacol. 1, 469–481 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Li, R., Coulthard, L. G., Wu, M. C. L., Taylor, S. M. & Woodruff, T. M. C5L2: a controversial receptor of complement anaphylatoxin, C5a. FASEB J. Publ. Fed. Am. Soc. Exp. Biol. 27, 855–864 (2013).

    CAS 

    Google Scholar 

  • Okinaga, S. et al. C5L2, a nonsignaling C5A binding protein. Biochemistry 42, 9406–9415 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sun, L. & Ye, R. D. Role of G protein-coupled receptors in inflammation. Acta Pharmacol. Sin. 33, 342–350 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wingler, L. M. & Lefkowitz, R. J. Conformational basis of G protein-coupled receptor signaling versatility. Trends Cell Biol. 30, 736–747 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Merle, N. S., Church, S. E., Fremeaux-Bacchi, V. & Roumenina, L. T. Complement system part I – molecular mechanisms of activation and regulation. Front. Immunol. 6, 262 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Buhl, A. M., Avdi, N., Worthen, G. S. & Johnson, G. L. Mapping of the C5a receptor signal transduction network in human neutrophils. Proc. Natl. Acad. Sci. USA 91, 9190–9194 (1994).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Perianayagam, M. C., Balakrishnan, V. S., King, A. J., Pereira, B. J. G. & Jaber, B. L. C5a delays apoptosis of human neutrophils by a phosphatidylinositol 3-kinase-signaling pathway. Kidney Int. 61, 456–463 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kastl, S. P. et al. The complement component C5a induces the expression of plasminogen activator inhibitor-1 in human macrophages via NF-kappaB activation. J. Thromb. Haemost. JTH 4, 1790–1797 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Torres, M. & Forman, H. J. Activation of several MAP kinases upon stimulation of rat alveolar macrophages: role of the NADPH oxidase. Arch. Biochem. Biophys. 366, 231–239 (1999).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Lo, R. K. H., Cheung, H. & Wong, Y. H. Constitutively active Galpha16 stimulates STAT3 via a c-Src/JAK- and ERK-dependent mechanism. J. Biol. Chem. 278, 52154–52165 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ye, R. D. Regulation of nuclear factor kappaB activation by G-protein-coupled receptors. J. Leukoc. Biol. 70, 839–848 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hajishengallis, G. & Lambris, J. D. More than complementing Tolls: complement-Toll-like receptor synergy and crosstalk in innate immunity and inflammation. Immunol. Rev. 274, 233–244 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bosmann, M. et al. Complement activation product C5a is a selective suppressor of TLR4-induced, but not TLR3-induced, production of IL-27(p28) from macrophages. J. Immunol. Baltim. Md 1950 188, 5086–5093 (2012).

    CAS 

    Google Scholar 

  • Hawlisch, H. et al. C5a negatively regulates toll-like receptor 4-induced immune responses. Immunity 22, 415–426 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Guo, Q. et al. NF-κB in biology and targeted therapy: new insights and translational implications. Signal Transduct. Target. Ther. 9, 53 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Arumugam, T. V. et al. Protective effect of a human C5a receptor antagonist against hepatic ischaemia-reperfusion injury in rats. J. Hepatol. 40, 934–941 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Schreiber, A. et al. C5a receptor mediates neutrophil activation and ANCA-induced glomerulonephritis. J. Am. Soc. Nephrol. JASN 20, 289–298 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Baelder, R. et al. Pharmacological targeting of anaphylatoxin receptors during the effector phase of allergic asthma suppresses airway hyperresponsiveness and airway inflammation. J. Immunol. Baltim. Md 1950 174, 783–789 (2005).

    CAS 

    Google Scholar 

  • Zlotnik, A., Yoshie, O. & Nomiyama, H. The chemokine and chemokine receptor superfamilies and their molecular evolution. Genome Biol. 7, 243 (2006).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Capucetti, A., Albano, F. & Bonecchi, R. Multiple roles for chemokines in neutrophil biology. Front. Immunol. 11, 1259 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bachelerie, F. et al. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors. Pharm. Rev. 66, 71P–79 (2013).

    Google Scholar 

  • Russo, R. C., Garcia, C. C., Teixeira, M. M. & Amaral, F. A. The CXCL8/IL-8 chemokine family and its receptors in inflammatory diseases. Expert Rev. Clin. Immunol. 10, 593–619 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Samanta, A. K., Oppenheim, J. J. & Matsushima, K. Identification and characterization of specific receptors for monocyte-derived neutrophil chemotactic factor (MDNCF) on human neutrophils. J. Exp. Med. 169, 1185–1189 (1989).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Granot, Z. et al. Tumor entrained neutrophils inhibit seeding in the premetastatic lung. Cancer Cell 20, 300–314 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • de Oliveira, T. H. C. et al. Intravital microscopic evaluation of the effects of a CXCR2 antagonist in a model of liver ischemia reperfusion injury in mice. Front. Immunol. 8, 1917 (2017).

    Article 
    PubMed 

    Google Scholar 

  • Nagarkar, D. R. et al. CXCR2 is required for neutrophilic airway inflammation and hyperresponsiveness in a mouse model of human rhinovirus infection. J. Immunol. Baltim. Md 1950 183, 6698–6707 (2009).

    CAS 

    Google Scholar 

  • Devalaraja, R. M. et al. Delayed wound healing in CXCR2 knockout mice. J. Invest. Dermatol. 115, 234–244 (2000).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bonnett, C. R., Cornish, E. J., Harmsen, A. G. & Burritt, J. B. Early neutrophil recruitment and aggregation in the murine lung inhibit germination of Aspergillus fumigatus Conidia. Infect. Immun. 74, 6528–6539 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Domínguez-Luis, M. J. et al. L-selectin expression is regulated by CXCL8-induced reactive oxygen species produced during human neutrophil rolling. Eur. J. Immunol. 49, 386–397 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Xu, R. et al. Low expression of CXCR1/2 on neutrophils predicts poor survival in patients with hepatitis B virus-related acute-on-chronic liver failure. Sci. Rep. 6, 38714 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hsieh, S.-C. et al. Abnormal in vitro CXCR2 modulation and defective cationic ion transporter expression on polymorphonuclear neutrophils responsible for hyporesponsiveness to IL-8 stimulation in patients with active systemic lupus erythematosus. Rheumatol. Oxf. Engl. 47, 150–157 (2008).

    Article 
    CAS 

    Google Scholar 

  • Bruserud, Ø., Mosevoll, K. A., Bruserud, Ø., Reikvam, H. & Wendelbo, Ø. The regulation of neutrophil migration in patients with sepsis: the complexity of the molecular mechanisms and their modulation in sepsis and the heterogeneity of sepsis patients. Cells 12, 1003 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Qiao, H. et al. CXCR2 Expression on neutrophils is upregulated during the relapsing phase of ocular Behcet disease. Curr. Eye Res. 30, 195–203 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kamohara, H., Takahashi, M., Ishiko, T., Ogawa, M. & Baba, H. Induction of interleukin-8 (CXCL-8) by tumor necrosis factor-alpha and leukemia inhibitory factor in pancreatic carcinoma cells: Impact of CXCL-8 as an autocrine growth factor. Int. J. Oncol. 31, 627–632 (2007).

    CAS 
    PubMed 

    Google Scholar 

  • Cheng, Y., Ma, X.-L., Wei, Y.-Q. & Wei, X.-W. Potential roles and targeted therapy of the CXCLs/CXCR2 axis in cancer and inflammatory diseases. Biochim. Biophys. Acta Rev. Cancer 1871, 289–312 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Montaño-Rendón, F., Grinstein, S. & Walpole, G. F. W. Monitoring phosphoinositide fluxes and effectors during leukocyte chemotaxis and phagocytosis. Front. Cell Dev. Biol. 9, 626136 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cheng, G. Z. et al. Advances of AKT pathway in human oncogenesis and as a target for anti-cancer drug discovery. Curr. Cancer Drug Targets 8, 2–6 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ha, H., Debnath, B. & Neamati, N. Role of the CXCL8-CXCR1/2 axis in cancer and inflammatory diseases. Theranostics 7, 1543–1588 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jamieson, T. et al. Inhibition of CXCR2 profoundly suppresses inflammation-driven and spontaneous tumorigenesis. J. Clin. Invest. 122, 3127–3144 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cataisson, C. et al. Inducible cutaneous inflammation reveals a protumorigenic role for keratinocyte CXCR2 in skin carcinogenesis. Cancer Res. 69, 319–328 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mestas, J. et al. The role of CXCR2/CXCR2 ligand biological axis in renal cell carcinoma. J. Immunol. Baltim. Md 1950 175, 5351–5357 (2005).

    CAS 

    Google Scholar 

  • Schiffmann, E., Corcoran, B. A. & Wahl, S. M. N-formylmethionyl peptides as chemoattractants for leucocytes. Proc. Natl. Acad. Sci. USA 72, 1059–1062 (1975).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hayashi, F., Means, T. K. & Luster, A. D. Toll-like receptors stimulate human neutrophil function. Blood 102, 2660–2669 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Dorward, D. A. et al. The role of formylated peptides and formyl peptide receptor 1 in governing neutrophil function during acute inflammation. Am. J. Pathol. 185, 1172–1184 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dai, Y., Major, J., Novotny, M. & Hamilton, T. A. IL-4 inhibits expression of the formyl peptide receptor gene in mouse peritoneal macrophages. J. Interferon Cytokine Res. J. Int. Soc. Interferon Cytokine Res. 25, 11–19 (2005).

    Article 

    Google Scholar 

  • Dahlgren, C., Gabl, M., Holdfeldt, A., Winther, M. & Forsman, H. Basic characteristics of the neutrophil receptors that recognize formylated peptides, a danger-associated molecular pattern generated by bacteria and mitochondria. Biochem. Pharmacol. 114, 22–39 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Loor, F., Tiberghien, F., Wenandy, T., Didier, A. & Traber, R. Cyclosporins: structure-activity relationships for the inhibition of the human FPR1 formylpeptide receptor. J. Med. Chem. 45, 4613–4628 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Li, S.-Q. et al. The expression of formyl peptide receptor 1 is correlated with tumor invasion of human colorectal cancer. Sci. Rep. 7, 5918 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Anton, P. A., Targan, S. R. & Shanahan, F. Increased neutrophil receptors for and response to the proinflammatory bacterial peptide formyl-methionyl-leucyl-phenylalanine in Crohn’s disease. Gastroenterology 97, 20–28 (1989).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Stockley, R. A., Grant, R. A., Llewellyn-Jones, C. G., Hill, S. L. & Burnett, D. Neutrophil formyl-peptide receptors. Relationship to peptide-induced responses and emphysema. Am. J. Respir. Crit. Care Med. 149, 464–468 (1994).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Cowland, J. B. & Borregaard, N. The individual regulation of granule protein mRNA levels during neutrophil maturation explains the heterogeneity of neutrophil granules. J. Leukoc. Biol. 66, 989–995 (1999).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sengeløv, H., Boulay, F., Kjeldsen, L. & Borregaard, N. Subcellular localization and translocation of the receptor for N-formylmethionyl-leucyl-phenylalanine in human neutrophils. Biochem. J. 299, 473–479 (1994).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chen, Y.-H., Wu, K.-H. & Wu, H.-P. Unraveling the complexities of toll-like receptors: from molecular mechanisms to clinical applications. Int. J. Mol. Sci. 25, 5037 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zindel, J. & Kubes, P. DAMPs, PAMPs, and LAMPs in immunity and sterile inflammation. Annu. Rev. Pathol. 15, 493–518 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Richard, K. et al. Dissociation of TRIF bias and adjuvanticity. Vaccine 38, 4298–4308 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yu, R., Zhu, B. & Chen, D. Type I interferon-mediated tumor immunity and its role in immunotherapy. Cell. Mol. Life Sci. CMLS 79, 191 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Andzinski, L. et al. Delayed apoptosis of tumor associated neutrophils in the absence of endogenous IFN-β. Int. J. Cancer 136, 572–583 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Jablonska, J., Wu, C.-F., Andzinski, L., Leschner, S. & Weiss, S. CXCR2-mediated tumor-associated neutrophil recruitment is regulated by IFN-β. Int. J. Cancer 134, 1346–1358 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Park, B. S. et al. The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature 458, 1191–1195 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Rajpoot, S. et al. TIRAP in the mechanism of inflammation. Front. Immunol. 12, 697588 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ciesielska, A., Matyjek, M. & Kwiatkowska, K. TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling. Cell. Mol. Life Sci. CMLS 78, 1233–1261 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Xu, G. et al. Virus-inducible IGFALS facilitates innate immune responses by mediating IRAK1 and TRAF6 activation. Cell. Mol. Immunol. 18, 1587–1589 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Strickson, S. et al. Roles of the TRAF6 and Pellino E3 ligases in MyD88 and RANKL signaling. Proc. Natl. Acad. Sci. USA 114, E3481–E3489 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ajibade, A. A., Wang, H. Y. & Wang, R.-F. Cell type-specific function of TAK1 in innate immune signaling. Trends Immunol. 34, 307–316 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Fukao, T. & Koyasu, S. PI3K and negative regulation of TLR signaling. Trends Immunol. 24, 358–363 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ha, T. et al. Lipopolysaccharide-induced myocardial protection against ischaemia/reperfusion injury is mediated through a PI3K/Akt-dependent mechanism. Cardiovasc. Res. 78, 546–553 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kim, G. O., Kim, N., Song, G. Y. & Bae, J.-S. Inhibitory activities of rare ginsenoside Rg4 on cecal ligation and puncture-induced sepsis. Int. J. Mol. Sci. 23, 10836 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yan, C. et al. Zhongfeng Capsules protects against cerebral ischemia-reperfusion injury via mediating the phosphoinositide 3-kinase/Akt and toll-like receptor 4/nuclear factor kappa B signaling pathways by regulating neuronal apoptosis and inflammation. Apoptosis Int. J. Program. Cell Death 27, 561–576 (2022).

    Article 
    CAS 

    Google Scholar 

  • Rosales, C. Neutrophils at the crossroads of innate and adaptive immunity. J. Leukoc. Biol. 108, 377–396 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Alemán, O. R. & Rosales, C. Human neutrophil Fc gamma receptors: different buttons for different responses. J. Leukoc. Biol. 114, 571–584 (2023).

    Article 
    PubMed 

    Google Scholar 

  • Chen, K. et al. Endocytosis of soluble immune complexes leads to their clearance by FcγRIIIB but induces neutrophil extracellular traps via FcγRIIA in vivo. Blood 120, 4421–4431 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Alemán, O. R., Mora, N., Cortes-Vieyra, R., Uribe-Querol, E. & Rosales, C. Transforming growth factor-β-Activated kinase 1 is required for human FcγRIIIb-induced neutrophil extracellular trap formation. Front. Immunol. 7, 277 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Behnen, M. et al. Immobilized immune complexes induce neutrophil extracellular trap release by human neutrophil granulocytes via FcγRIIIB and Mac-1. J. Immunol. Baltim. Md 1950 193, 1954–1965 (2014).

    CAS 

    Google Scholar 

  • Alemán, O. R., Mora, N., Cortes-Vieyra, R., Uribe-Querol, E. & Rosales, C. Differential use of human neutrophil Fcγ receptors for inducing neutrophil extracellular trap formation. J. Immunol. Res. 2016, 2908034 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Alemán, O. R., Mora, N. & Rosales, C. The antibody receptor Fc gamma receptor IIIb induces calcium entry via transient receptor potential melastatin 2 in human neutrophils. Front. Immunol. 12, 657393 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Golay, J. et al. Human neutrophils express low levels of FcγRIIIA, which plays a role in PMN activation. Blood 133, 1395–1405 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Treffers, L. W. et al. FcγRIIIb restricts antibody-dependent destruction of cancer cells by human neutrophils. Front. Immunol. 9, 3124 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bournazos, S. & Ravetch, J. V. Fcγ receptor pathways during active and passive immunization. Immunol. Rev. 268, 88–103 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, Y. & Jönsson, F. Expression, role, and regulation of neutrophil fcγ receptors. Front. Immunol. 10, 1958 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Vogt, K. L., Summers, C., Chilvers, E. R. & Condliffe, A. M. Priming and de-priming of neutrophil responses in vitro and in vivo. Eur. J. Clin. Invest. 48, e12967 (2018).

    Article 
    PubMed 

    Google Scholar 

  • Khor, C. C. et al. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. Nat. Genet. 43, 1241–1246 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Shrestha, S. et al. Role of activating FcγR gene polymorphisms in Kawasaki disease susceptibility and intravenous immunoglobulin response. Circ. Cardiovasc. Genet. 5, 309–316 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Nagelkerke, S. Q. et al. Extensive ethnic variation and linkage disequilibrium at the FCGR2/3 locus: different genetic associations revealed in Kawasaki disease. Front. Immunol. 10, 185 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Perdomo, J. et al. Neutrophil activation and NETosis are the major drivers of thrombosis in heparin-induced thrombocytopenia. Nat. Commun. 10, 1322 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhang, Q., Li, W., Mao, X. & Miao, S. Platelet FcγRIIA: an emerging regulator and biomarker in cardiovascular disease and cancer. Thromb. Res. 238, 19–26 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Treffers, L. W. et al. Genetic variation of human neutrophil Fcγ receptors and SIRPα in antibody-dependent cellular cytotoxicity towards cancer cells. Eur. J. Immunol. 48, 344–354 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Musolino, A. et al. Role of Fcγ receptors in HER2-targeted breast cancer therapy. J. Immunother. Cancer 10, e003171 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Caratelli, S. et al. In vitro elimination of epidermal growth factor receptor-overexpressing cancer cells by CD32A-chimeric receptor T cells in combination with cetuximab or panitumumab. Int. J. Cancer 146, 236–247 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zeng, Q. et al. Recent advances in hematopoietic cell kinase in cancer progression: Mechanisms and inhibitors. Biomed. Pharmacother. Biomed. Pharmacother. 176, 116932 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Peterson, C. & Chandler, H. L. Insulin facilitates corneal wound healing in the diabetic environment through the RTK-PI3K/Akt/mTOR axis in vitro. Mol. Cell. Endocrinol. 548, 111611 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hunter, T. Discovering the first tyrosine kinase. Proc. Natl. Acad. Sci. USA 112, 7877–7882 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Stakenborg, M. et al. Neutrophilic HGF-MET signalling exacerbates intestinal inflammation. J. Crohns Colitis 14, 1748–1758 (2020).

    Article 
    PubMed 

    Google Scholar 

  • Felix, F. B. et al. Blocking the HGF-MET pathway induces resolution of neutrophilic inflammation by promoting neutrophil apoptosis and efferocytosis. Pharmacol. Res. 188, 106640 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Lombardi, A. M., Sangiolo, D. & Vigna, E. MET oncogene targeting for cancer immunotherapy. Int. J. Mol. Sci. 25, 6109 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Finisguerra, V. et al. MET is required for the recruitment of anti-tumoural neutrophils. Nature 522, 349–353 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Glodde, N. et al. Reactive neutrophil responses dependent on the receptor tyrosine kinase c-MET limit cancer immunotherapy. Immunity 47, 789–802.e9 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Futosi, K. et al. Dasatinib inhibits proinflammatory functions of mature human neutrophils. Blood 119, 4981–4991 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wu, Y., Hannigan, M., Zhan, L., Madri, J. A. & Huang, C.-K.- NOD mice having a lyn tyrosine kinase mutation exhibit abnormal neutrophil chemotaxis. J. Cell. Physiol. 232, 1689–1695 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Mazzi, P., Caveggion, E., Lapinet-Vera, J. A., Lowell, C. A. & Berton, G. The Src-family kinases Hck and Fgr regulate early lipopolysaccharide-induced myeloid cell recruitment into the lung and their ability to secrete chemokines. J. Immunol. Baltim. Md 1950 195, 2383–2395 (2015).

    CAS 

    Google Scholar 

  • Lőrincz, Á. M. et al. Different calcium and Src family kinase signaling in Mac-1 dependent phagocytosis and extracellular vesicle generation. Front. Immunol. 10, 2942 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Futosi, K. et al. Myeloid Src-family kinases are critical for neutrophil-mediated autoinflammation in gout and motheaten models. J. Exp. Med. 220, e20221010 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Liao, H.-R., Kao, Y.-Y., Leu, Y.-L., Liu, F.-C. & Tseng, C.-P. Larixol inhibits fMLP-induced superoxide anion production and chemotaxis by targeting the βγ subunit of Gi-protein of fMLP receptor in human neutrophils. Biochem. Pharmacol. 201, 115091 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Cheung, R. et al. An arrestin-dependent multi-kinase signaling complex mediates MIP-1beta/CCL4 signaling and chemotaxis of primary human macrophages. J. Leukoc. Biol. 86, 833–845 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lowell, C. A. Src-family and Syk kinases in activating and inhibitory pathways in innate immune cells: signaling cross talk. Cold Spring Harb. Perspect. Biol. 3, a002352 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jakus, Z., Németh, T., Verbeek, J. S. & Mócsai, A. Critical but overlapping role of FcgammaRIII and FcgammaRIV in activation of murine neutrophils by immobilized immune complexes. J. Immunol. Baltim. Md 1950 180, 618–629 (2008).

    CAS 

    Google Scholar 

  • Negoro, P. E. et al. Spleen tyrosine kinase is a critical regulator of neutrophil responses to candida species. mBio. 11, e02043–19 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Nguyen, G. T. et al. SKAP2 is required for defense against K. pneumoniae infection and neutrophil respiratory burst. eLife 9, e56656 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhou, Q. et al. Syk-dependent homologous recombination activation promotes cancer resistance to DNA targeted therapy. Drug Resist. Updat. Rev. Comment. Antimicrob. Anticancer Chemother. 74, 101085 (2024).

    CAS 

    Google Scholar 

  • Tanimura, S. & Takeda, K. ERK signalling as a regulator of cell motility. J. Biochem. (Tokyo) 162, 145–154 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wang, D. et al. The configuration of GRB2 in protein interaction and signal transduction. Biomolecules 14, 259 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bahar, M. E., Kim, H. J. & Kim, D. R. Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies. Signal Transduct. Target. Ther. 8, 455 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rickert, P., Weiner, O. D., Wang, F., Bourne, H. R. & Servant, G. Leukocytes navigate by compass: roles of PI3Kgamma and its lipid products. Trends Cell Biol. 10, 466–473 (2000).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hirsch, E. et al. Signaling through PI3Kgamma: a common platform for leukocyte, platelet and cardiovascular stress sensing. Thromb. Haemost. 95, 29–35 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sánchez-Madrid, F. & del Pozo, M. A. Leukocyte polarization in cell migration and immune interactions. EMBO J. 18, 501–511 (1999).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cotton, M. & Claing, A. G protein-coupled receptors stimulation and the control of cell migration. Cell. Signal. 21, 1045–1053 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Rathinaswamy, M. K. et al. HDX-MS-optimized approach to characterize nanobodies as tools for biochemical and structural studies of class IB phosphoinositide 3-kinases. Struct. Lond. Engl. 1993 29, 1371–1381.e6 (2021).

    CAS 

    Google Scholar 

  • Sasaki, A. T., Chun, C., Takeda, K. & Firtel, R. A. Localized Ras signaling at the leading edge regulates PI3K, cell polarity, and directional cell movement. J. Cell Biol. 167, 505–518 (2004).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yang, H., Wang, C., Zhang, L., Lv, J. & Ni, H. Rutin alleviates hypoxia/reoxygenation-induced injury in myocardial cells by up-regulating SIRT1 expression. Chem. Biol. Interact. 297, 44–49 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Maehama, T. & Dixon, J. E. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J. Biol. Chem. 273, 13375–13378 (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Heit, B. et al. PTEN functions to ‘prioritize’ chemotactic cues and prevent ‘distraction’ in migrating neutrophils. Nat. Immunol. 9, 743–752 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Dong, X. et al. P-Rex1 is a primary Rac2 guanine nucleotide exchange factor in mouse neutrophils. Curr. Biol. CB 15, 1874–1879 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Li, Z. et al. Directional sensing requires G beta gamma-mediated PAK1 and PIX alpha-dependent activation of Cdc42. Cell 114, 215–227 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Xu, J. et al. Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. Cell 114, 201–214 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hall, A. Rho GTPases and the actin cytoskeleton. Science 279, 509–514 (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Strzelecka-Kiliszek, A. et al. Functions of Rho family of small GTPases and Rho-associated coiled-coil kinases in bone cells during differentiation and mineralization. Biochim. Biophys. Acta Gen. Subj. 1861, 1009–1023 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Xu, X. & Yao, L. Recent advances in the development of Rho kinase inhibitors (2015-2021). Med. Res. Rev. 44, 406–421 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Miki, H., Suetsugu, S. & Takenawa, T. WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac. EMBO J. 17, 6932–6941 (1998).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Weiner, O. D. et al. Hem-1 complexes are essential for Rac activation, actin polymerization, and myosin regulation during neutrophil chemotaxis. PLoS Biol. 4, e38 (2006).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dey, S. & Zhou, H.-X. Why does synergistic activation of WASP, but Not N-WASP, by Cdc42 and PIP2 require Cdc42 prenylation? J. Mol. Biol. 435, 168035 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Labrosse, R. et al. Outcomes of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome. Blood 142, 1281–1296 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, F. The signaling mechanisms underlying cell polarity and chemotaxis. Cold Spring Harb. Perspect. Biol. 1, a002980 (2009).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dixit, N. & Simon, S. I. Chemokines, selectins and intracellular calcium flux: temporal and spatial cues for leukocyte arrest. Front. Immunol. 3, 188 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bagur, R. & Hajnóczky, G. Intracellular Ca2+ sensing: its role in calcium homeostasis and signaling. Mol. Cell 66, 780–788 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Feske, S., Wulff, H. & Skolnik, E. Y. Ion channels in innate and adaptive immunity. Annu. Rev. Immunol. 33, 291–353 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Banoth, B. & Cassel, S. L. Mitochondria in innate immune signaling. Transl. Res. J. Lab. Clin. Med. 202, 52–68 (2018).

    CAS 

    Google Scholar 

  • Watson, J. L. et al. Synthetic Par polarity induces cytoskeleton asymmetry in unpolarized mammalian cells. Cell 186, 4710–4727.e35 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Schaff, U. Y. et al. Calcium flux in neutrophils synchronizes beta2 integrin adhesive and signaling events that guide inflammatory recruitment. Ann. Biomed. Eng. 36, 632–646 (2008).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lindemann, O. et al. TRPC6 regulates CXCR2-mediated chemotaxis of murine neutrophils. J. Immunol. Baltim. Md 1950 190, 5496–5505 (2013).

    CAS 

    Google Scholar 

  • Downey, G. P. et al. Biophysical properties and microfilament assembly in neutrophils: modulation by cyclic AMP. J. Cell Biol. 114, 1179–1190 (1991).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Nagata, S., Kebo, D. K., Kunkel, S. & Glovsky, M. M. Effect of adenylate cyclase activators on C5a-induced human neutrophil aggregation, enzyme release and superoxide production. Int. Arch. Allergy Immunol. 97, 194–199 (1992).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • del Pozo, M. A., Sánchez-Mateos, P., Nieto, M. & Sánchez-Madrid, F. Chemokines regulate cellular polarization and adhesion receptor redistribution during lymphocyte interaction with endothelium and extracellular matrix. Involvement of cAMP signaling pathway. J. Cell Biol. 131, 495–508 (1995).

    Article 
    PubMed 

    Google Scholar 

  • Li, H. et al. Association between Gαi2 and ELMO1/Dock180 connects chemokine signalling with Rac activation and metastasis. Nat. Commun. 4, 1706 (2013).

    Article 
    PubMed 

    Google Scholar 

  • Kamp, M. E., Liu, Y. & Kortholt, A. Function and Regulation of Heterotrimeric G Proteins during Chemotaxis. Int. J. Mol. Sci. 17, 90 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • De Vries, L. et al. Activator of G protein signaling 3 is a guanine dissociation inhibitor for Galpha I subunits. Proc. Natl Acad. Sci. Usa. 97, 14364–14369 (2000).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kamakura, S. et al. The cell polarity protein mInsc regulates neutrophil chemotaxis via a noncanonical G protein signaling pathway. Dev. Cell 26, 292–302 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wu, J. et al. Homer3 regulates the establishment of neutrophil polarity. Mol. Biol. Cell 26, 1629–1639 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Essler, M. et al. Thrombin inactivates myosin light chain phosphatase via Rho and its target Rho kinase in human endothelial cells. J. Biol. Chem. 273, 21867–21874 (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Gan, X. et al. PRR5L degradation promotes mTORC2-mediated PKC-δ phosphorylation and cell migration downstream of Gα12. Nat. Cell Biol. 14, 686–696 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Nürnberg, B., Beer-Hammer, S., Reisinger, E. & Leiss, V. Non-canonical G protein signaling. Pharmacol. Ther. 255, 108589 (2024).

    Article 
    PubMed 

    Google Scholar 

  • Liu, Y. et al. The regulatory role of PI3K in ageing-related diseases. Ageing Res. Rev. 88, 101963 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hirsch, E. et al. Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Science 287, 1049–1053 (2000).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Schindler, J. F., Monahan, J. B. & Smith, W. G. p38 pathway kinases as anti-inflammatory drug targets. J. Dent. Res. 86, 800–811 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Jiang, Y. et al. Structure-function studies of p38 mitogen-activated protein kinase. Loop 12 influences substrate specificity and autophosphorylation, but not upstream kinase selection. J. Biol. Chem. 272, 11096–11102 (1997).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zhang, Y. L. & Dong, C. MAP kinases in immune responses. Cell. Mol. Immunol. 2, 20–27 (2005).

    CAS 
    PubMed 

    Google Scholar 

  • Wennerberg, K., Rossman, K. L. & Der, C. J. The Ras superfamily at a glance. J. Cell Sci. 118, 843–846 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Raman, M., Chen, W. & Cobb, M. H. Differential regulation and properties of MAPKs. Oncogene 26, 3100–3112 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Cambier, S., Gouwy, M. & Proost, P. The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention. Cell. Mol. Immunol. 20, 217–251 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chardin, P., Cussac, D., Maignan, S. & Ducruix, A. The Grb2 adaptor. FEBS Lett. 369, 47–51 (1995).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Nickerson, S., Joy, S. T., Arora, P. S. & Bar-Sagi, D. An orthosteric inhibitor of the RAS-SOS interaction. Enzymes 34 Pt. B, 25–39 (2013).

    Article 
    PubMed 

    Google Scholar 

  • Downward, J. Control of ras activation. Cancer Surv. 27, 87–100 (1996).

    CAS 
    PubMed 

    Google Scholar 

  • Scolnick, E. M., Papageorge, A. G. & Shih, T. Y. Guanine nucleotide-binding activity as an assay for src protein of rat-derived murine sarcoma viruses. Proc. Natl. Acad. Sci. USA 76, 5355–5359 (1979).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mitin, N., Rossman, K. L. & Der, C. J. Signaling interplay in Ras superfamily function. Curr. Biol. CB 15, R563–574 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ersahin, T., Tuncbag, N. & Cetin-Atalay, R. The PI3K/AKT/mTOR interactive pathway. Mol. Biosyst. 11, 1946–1954 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Fedorenko, I. V., Paraiso, K. H. T. & Smalley, K. S. M. Acquired and intrinsic BRAF inhibitor resistance in BRAF V600E mutant melanoma. Biochem. Pharmacol. 82, 201–209 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kolch, W. Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions. Biochem. J. 351 Pt 2, 289–305 (2000).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Carey, K. D., Watson, R. T., Pessin, J. E. & Stork, P. J. S. The requirement of specific membrane domains for Raf-1 phosphorylation and activation. J. Biol. Chem. 278, 3185–3196 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zhang, Y. & Dong, C. Regulatory mechanisms of mitogen-activated kinase signaling. Cell. Mol. Life Sci. CMLS 64, 2771–2789 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Avruch, J. et al. Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase cascade. Recent Prog. Horm. Res. 56, 127–155 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Campellone, K. G. & Welch, M. D. A nucleator arms race: cellular control of actin assembly. Nat. Rev. Mol. Cell Biol. 11, 237–251 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Reinhard, M., Jarchau, T. & Walter, U. Actin-based motility: stop and go with Ena/VASP proteins. Trends Biochem. Sci. 26, 243–249 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Takenawa, T. & Suetsugu, S. The WASP-WAVE protein network: connecting the membrane to the cytoskeleton. Nat. Rev. Mol. Cell Biol. 8, 37–48 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Danson, C. M., Pocha, S. M., Bloomberg, G. B. & Cory, G. O. Phosphorylation of WAVE2 by MAP kinases regulates persistent cell migration and polarity. J. Cell Sci. 120, 4144–4154 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Mendoza, M. C. et al. ERK-MAPK drives lamellipodia protrusion by activating the WAVE2 regulatory complex. Mol. Cell 41, 661–671 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Martinez-Quiles, N., Ho, H.-Y. H., Kirschner, M. W., Ramesh, N. & Geha, R. S. Erk/Src phosphorylation of cortactin acts as a switch on-switch off mechanism that controls its ability to activate N-WASP. Mol. Cell. Biol. 24, 5269–5280 (2004).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tcherkezian, J., Danek, E. I., Jenna, S., Triki, I. & Lamarche-Vane, N. Extracellular signal-regulated kinase 1 interacts with and phosphorylates CdGAP at an important regulatory site. Mol. Cell. Biol. 25, 6314–6329 (2005).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Campbell, J. J., Foxman, E. F. & Butcher, E. C. Chemoattractant receptor cross talk as a regulatory mechanism in leukocyte adhesion and migration. Eur. J. Immunol. 27, 2571–2578 (1997).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Heit, B., Liu, L., Colarusso, P., Puri, K. D. & Kubes, P. PI3K accelerates, but is not required for, neutrophil chemotaxis to fMLP. J. Cell Sci. 121, 205–214 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Heit, B., Tavener, S., Raharjo, E. & Kubes, P. An intracellular signaling hierarchy determines direction of migration in opposing chemotactic gradients. J. Cell Biol. 159, 91–102 (2002).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Khan, A. I. & Kubes, P. L-selectin: an emerging player in chemokine function. Microcirc. N. Y. N. 1994 10, 351–358 (2003).

    CAS 

    Google Scholar 

  • Roberts-Crowley, M. L., Mitra-Ganguli, T., Liu, L. & Rittenhouse, A. R. Regulation of voltage-gated Ca2+ channels by lipids. Cell Calcium 45, 589–601 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Philips, R. L. et al. The JAK-STAT pathway at 30: Much learned, much more to do. Cell 185, 3857–3876 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hu, X., Li, J., Fu, M., Zhao, X. & Wang, W. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct. Target. Ther. 6, 402 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Xin, P. et al. The role of JAK/STAT signaling pathway and its inhibitors in diseases. Int. Immunopharmacol. 80, 106210 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Coricello, A., Mesiti, F., Lupia, A., Maruca, A. & Alcaro, S. Inside perspective of the synthetic and computational toolbox of JAK inhibitors: recent updates. Mol. Basel Switz. 25, 3321 (2020).

    CAS 

    Google Scholar 

  • Durham, G. A., Williams, J. J. L., Nasim, M. T. & Palmer, T. M. Targeting SOCS proteins to control JAK-STAT signalling in disease. Trends Pharmacol. Sci. 40, 298–308 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • O’Shea, J. J. et al. The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu. Rev. Med. 66, 311–328 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Li, H. S. & Watowich, S. S. Innate immune regulation by STAT-mediated transcriptional mechanisms. Immunol. Rev. 261, 84–101 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wilmes, S. et al. Mechanism of homodimeric cytokine receptor activation and dysregulation by oncogenic mutations. Science 367, 643–652 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Saleiro, D. & Platanias, L. C. Interferon signaling in cancer. Non-canonical pathways and control of intracellular immune checkpoints. Semin. Immunol. 43, 101299 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lazear, H. M., Nice, T. J. & Diamond, M. S. Interferon-λ: immune functions at barrier surfaces and beyond. Immunity 43, 15–28 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Parker, B. S., Rautela, J. & Hertzog, P. J. Antitumour actions of interferons: implications for cancer therapy. Nat. Rev. Cancer 16, 131–144 (2016).

    Article 
    PubMed 

    Google Scholar 

  • Lazear, H. M., Schoggins, J. W. & Diamond, M. S. Shared and distinct functions of type I and type III interferons. Immunity 50, 907–923 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Platanitis, E. et al. A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription. Nat. Commun. 10, 2921 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Stegelmeier, A. A. et al. Type I interferon-mediated regulation of antiviral capabilities of neutrophils. Int. J. Mol. Sci. 22, 4726 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mahlakõiv, T., Hernandez, P., Gronke, K., Diefenbach, A. & Staeheli, P. Leukocyte-derived IFN-α/β and epithelial IFN-λ constitute a compartmentalized mucosal defense system that restricts enteric virus infections. PLoS Pathog. 11, e1004782 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hernández, P. P. et al. Interferon-λ and interleukin 22 act synergistically for the induction of interferon-stimulated genes and control of rotavirus infection. Nat. Immunol. 16, 698–707 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Schoggins, J. W. et al. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 472, 481–485 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ambler, W. G. & Kaplan, M. J. Vascular damage in systemic lupus erythematosus. Nat. Rev. Nephrol. 20, 251–265 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Jablonska, J., Leschner, S., Westphal, K., Lienenklaus, S. & Weiss, S. Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model. J. Clin. Invest. 120, 1151–1164 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Garcia-Diaz, A. et al. Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression. Cell Rep. 19, 1189–1201 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Du, W., Frankel, T. L., Green, M. & Zou, W. IFNγ signaling integrity in colorectal cancer immunity and immunotherapy. Cell. Mol. Immunol. 19, 23–32 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Castro, F., Cardoso, A. P., Gonçalves, R. M., Serre, K. & Oliveira, M. J. Interferon-gamma at the crossroads of tumor immune surveillance or evasion. Front. Immunol. 9, 847 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Purbey, P. K. et al. Opposing tumor-cell-intrinsic and -extrinsic roles of the IRF1 transcription factor in antitumor immunity. Cell Rep. 43, 114289 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yan, Y., Zheng, L., Du, Q., Yan, B. & Geller, D. A. Interferon regulatory factor 1 (IRF-1) and IRF-2 regulate PD-L1 expression in hepatocellular carcinoma (HCC) cells. Cancer Immunol. Immunother. CII 69, 1891–1903 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Teng, H.-W. et al. Interferon gamma induces higher neutrophil extracellular traps leading to tumor-killing activity in microsatellite stable colorectal cancer. Mol. Cancer Ther. 23, 1043–1056 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ye, L., Schnepf, D. & Staeheli, P. Interferon-λ orchestrates innate and adaptive mucosal immune responses. Nat. Rev. Immunol. 19, 614–625 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Espinosa, V. et al. Type III interferon is a critical regulator of innate antifungal immunity. Sci. Immunol. 2, eaan5357 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Philip, D. T. et al. Interferon lambda restricts herpes simplex virus skin disease by suppressing neutrophil-mediated pathology. mBio. 15, e0262323 (2024).

    Article 
    PubMed 

    Google Scholar 

  • Landy, E., Carol, H., Ring, A. & Canna, S. Biological and clinical roles of IL-18 in inflammatory diseases. Nat. Rev. Rheumatol. 20, 33–47 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Song, M., Tang, Y., Cao, K., Qi, L. & Xie, K. Unveiling the role of interleukin-6 in pancreatic cancer occurrence and progression. Front. Endocrinol. 15, 1408312 (2024).

    Article 

    Google Scholar 

  • Lederle, W. et al. IL-6 promotes malignant growth of skin SCCs by regulating a network of autocrine and paracrine cytokines. Int. J. Cancer 128, 2803–2814 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hunter, C. A. & Jones, S. A. IL-6 as a keystone cytokine in health and disease. Nat. Immunol. 16, 448–457 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Johnson, D. E., O’Keefe, R. A. & Grandis, J. R. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat. Rev. Clin. Oncol. 15, 234–248 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cimica, V., Chen, H.-C., Iyer, J. K. & Reich, N. C. Dynamics of the STAT3 transcription factor: nuclear import dependent on Ran and importin-β1. PloS One 6, e20188 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kang, S., Tanaka, T., Narazaki, M. & Kishimoto, T. Targeting Interleukin-6 Signaling in Clinic. Immunity 50, 1007–1023 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Shang, A. et al. Long non-coding RNA HOTTIP enhances IL-6 expression to potentiate immune escape of ovarian cancer cells by upregulating the expression of PD-L1 in neutrophils. J. Exp. Clin. Cancer Res. CR 38, 411 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Lauber, S. et al. Novel function of Oncostatin M as a potent tumour-promoting agent in lung. Int. J. Cancer 136, 831–843 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Masjedi, A. et al. Oncostatin M: a mysterious cytokine in cancers. Int. Immunopharmacol. 90, 107158 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Queen, M. M., Ryan, R. E., Holzer, R. G., Keller-Peck, C. R. & Jorcyk, C. L. Breast cancer cells stimulate neutrophils to produce oncostatin M: potential implications for tumor progression. Cancer Res. 65, 8896–8904 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zhou, Z. et al. Tumor-associated neutrophils and macrophages interaction contributes to intrahepatic cholangiocarcinoma progression by activating STAT3. J. Immunother. Cancer 9, e001946 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Singer, M. et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315, 801–810 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Adrover, J. M. et al. Programmed ‘disarming’ of the neutrophil proteome reduces the magnitude of inflammation. Nat. Immunol. 21, 135–144 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sônego, F. et al. Paradoxical roles of the neutrophil in sepsis: protective and deleterious. Front. Immunol. 7, 155 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Qi, Y. et al. Microfluidic device reveals new insights into impairment of neutrophil transmigration in patients with sepsis. Biosens. Bioelectron. 260, 116460 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wang, J.-F. et al. Up-regulation of programmed cell death 1 ligand 1 on neutrophils may be involved in sepsis-induced immunosuppression: an animal study and a prospective case-control study. Anesthesiology 122, 852–863 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Alves-Filho, J. C. et al. Regulation of chemokine receptor by Toll-like receptor 2 is critical to neutrophil migration and resistance to polymicrobial sepsis. Proc. Natl. Acad. Sci. USA 106, 4018–4023 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Souto, F. O. et al. Essential role of CCR2 in neutrophil tissue infiltration and multiple organ dysfunction in sepsis. Am. J. Respir. Crit. Care Med. 183, 234–242 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zhang, H. et al. Neutrophil, neutrophil extracellular traps and endothelial cell dysfunction in sepsis. Clin. Transl. Med. 13, e1170 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Engelmann, B. & Massberg, S. Thrombosis as an intravascular effector of innate immunity. Nat. Rev. Immunol. 13, 34–45 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • McDonald, B. et al. Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice. Blood 129, 1357–1367 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • von Brühl, M.-L. et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J. Exp. Med. 209, 819–835 (2012).

    Article 

    Google Scholar 

  • Chen, Z. et al. Review: the emerging role of neutrophil extracellular traps in sepsis and sepsis-associated thrombosis. Front. Cell. Infect. Microbiol. 11, 653228 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Joffre, J., Hellman, J., Ince, C. & Ait-Oufella, H. Endothelial responses in sepsis. Am. J. Respir. Crit. Care Med. 202, 361–370 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Anaya, D. A. & Dellinger, E. P. Necrotizing soft-tissue infection: diagnosis and management. Clin. Infect. Dis. Publ. Infect. Dis. Soc. Am. 44, 705–710 (2007).

    Article 
    CAS 

    Google Scholar 

  • Gabillot-Carré, M. & Roujeau, J.-C. Acute bacterial skin infections and cellulitis. Curr. Opin. Infect. Dis. 20, 118–123 (2007).

    Article 
    PubMed 

    Google Scholar 

  • Stevens, D. L. & Bryant, A. E. Necrotizing soft-tissue infections. N. Engl. J. Med. 377, 2253–2265 (2017).

    Article 
    PubMed 

    Google Scholar 

  • Hidalgo-Grass, C. et al. A streptococcal protease that degrades CXC chemokines and impairs bacterial clearance from infected tissues. EMBO J. 25, 4628–4637 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Pinho-Ribeiro, F. A. et al. Blocking neuronal signaling to immune cells treats streptococcal invasive infection. Cell 173, 1083–1097.e22 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Borschitz, T., Schlicht, S., Siegel, E., Hanke, E. & von Stebut, E. Improvement of a clinical score for necrotizing fasciitis: ‘pain out of proportion’ and high CRP levels aid the diagnosis. PloS One 10, e0132775 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cui, J., Li, F. & Shi, Z.-L. Origin and evolution of pathogenic coronaviruses. Nat. Rev. Microbiol. 17, 181–192 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Loyer, C. et al. Impairment of neutrophil functions and homeostasis in COVID-19 patients: association with disease severity. Crit. Care 26, 155 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Pastorek, M., Dúbrava, M. & Celec, P. On the origin of neutrophil extracellular traps in COVID-19. Front. Immunol. 13, 821007 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chen, R. et al. Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China. J. Allergy Clin. Immunol. 146, 89–100 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Barnes, B. J. et al. Targeting potential drivers of COVID-19: neutrophil extracellular traps. J. Exp. Med. 217, e20200652 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bourgonje, A. R. et al. Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). J. Pathol. 251, 228–248 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Clark, D., Kotronia, E. & Ramsay, S. E. Frailty, aging, and periodontal disease: basic biologic considerations. Periodontol 2000 87, 143–156 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cabrera, L. E. et al. Characterization of low-density granulocytes in COVID-19. PLoS Pathog. 17, e1009721 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Obermayer, A. et al. Neutrophil extracellular traps in fatal COVID-19-associated lung injury. Dis. Markers 2021, 5566826 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Thierry, A. R. & Roch, B. Neutrophil extracellular traps and by-products play a key role in COVID-19: pathogenesis, risk factors, and therapy. J. Clin. Med. 9, 2942 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Janiuk, K., Jabłońska, E. & Garley, M. Significance of NETs formation in COVID-19. Cells 10, 151 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Behzadifard, M. & Soleimani, M. NETosis and SARS-COV-2 infection related thrombosis: a narrative review. Thromb. J. 20, 13 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gorochov, G. et al. Serum and salivary IgG and IgA response after COVID-19 messenger RNA vaccination. JAMA Netw. Open 7, e248051 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Primorac Padjen, E. et al. Comparison of reporting rates of arthritis and arthralgia following AstraZeneca, Pfizer-BioNTech, Moderna, and Janssen vaccine administration against SARS-CoV-2 in 2021: analysis of European pharmacovigilance large-scale data. Rheumatol. Int. 44, 273–281 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Siyer, O., Aksakal, B. & Basat, S. Evaluation of the effects of anakinra treatment on clinic and laboratory results in patients with COVID-19. North. Clin. Istanb. 10, 189–196 (2023).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Morán, G., Uberti, B. & Quiroga, J. Role of cellular metabolism in the formation of neutrophil extracellular traps in airway diseases. Front. Immunol. 13, 850416 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dalbeth, N., Merriman, T. R. & Stamp, L. K. Gout. Lancet Lond. Engl. 388, 2039–2052 (2016).

    Article 
    CAS 

    Google Scholar 

  • So, A. K. & Martinon, F. Inflammation in gout: mechanisms and therapeutic targets. Nat. Rev. Rheumatol. 13, 639–647 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Martinon, F. & Glimcher, L. H. Gout: new insights into an old disease. J. Clin. Invest. 116, 2073–2075 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chen, C.-J. et al. MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals. J. Clin. Invest. 116, 2262–2271 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Popa-Nita, O. & Naccache, P. H. Crystal-induced neutrophil activation. Immunol. Cell Biol. 88, 32–40 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Fernandes, M. J. & Naccache, P. H. The role of inhibitory receptors in monosodium urate crystal-induced inflammation. Front. Immunol. 9, 1883 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Abhishek, A., Roddy, E. & Doherty, M. Gout – a guide for the general and acute physicians. Clin. Med. Lond. Engl. 17, 54–59 (2017).

    Article 

    Google Scholar 

  • Tan, H., Li, Z., Zhang, S., Zhang, J. & Jia, E. Novel perception of neutrophil extracellular traps in gouty inflammation. Int. Immunopharmacol. 115, 109642 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Cohen, R. E., Pillinger, M. H. & Toprover, M. Something old, something new: the ACR gout treatment guideline and its evolution from 2012 to 2020. Curr. Rheumatol. Rep. 23, 4 (2020).

    Article 
    PubMed 

    Google Scholar 

  • Peng, X. et al. Gout therapeutics and drug delivery. J. Control. Release J. Control. Release Soc. 362, 728–754 (2023).

    Article 
    CAS 

    Google Scholar 

  • Manrique-Acevedo, C., Hirsch, I. B. & Eckel, R. H. Prevention of cardiovascular disease in type 1 diabetes. N. Engl. J. Med. 390, 1207–1217 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Giovenzana, A., Carnovale, D., Phillips, B., Petrelli, A. & Giannoukakis, N. Neutrophils and their role in the aetiopathogenesis of type 1 and type 2 diabetes. Diabetes Metab. Res. Rev. 38, e3483 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Silvestre-Roig, C., Braster, Q., Ortega-Gomez, A. & Soehnlein, O. Neutrophils as regulators of cardiovascular inflammation. Nat. Rev. Cardiol. 17, 327–340 (2020).

    Article 
    PubMed 

    Google Scholar 

  • Talukdar, S. et al. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat. Med. 18, 1407–1412 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Watanabe, Y. et al. Bidirectional crosstalk between neutrophils and adipocytes promotes adipose tissue inflammation. FASEB J. Publ. Fed. Am. Soc. Exp. Biol. 33, 11821–11835 (2019).

    CAS 

    Google Scholar 

  • Bae, S. et al. Neutrophil proteinase 3 induces diabetes in a mouse model of glucose tolerance. Endocr. Res. 37, 35–45 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Valle, A. et al. Reduction of circulating neutrophils precedes and accompanies type 1 diabetes. Diabetes 62, 2072–2077 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bollyky, J. B. et al. Heterogeneity in recent-onset type 1 diabetes – a clinical trial perspective. Diabetes Metab. Res. Rev. 31, 588–594 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Doğruel, H., Aydemir, M. & Balci, M. K. Management of diabetic foot ulcers and the challenging points: An endocrine view. World J. Diabetes 13, 27–36 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Armstrong, D. G., Tan, T.-W., Boulton, A. J. M. & Bus, S. A. Diabetic foot ulcers: a review. JAMA 330, 62–75 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gauer, J. S., Ajjan, R. A. & Ariëns, R. A. S. Platelet-neutrophil interaction and thromboinflammation in diabetes: considerations for novel therapeutic approaches. J. Am. Heart Assoc. 11, e027071 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Giannella, A. et al. PAR-4/Ca2+-calpain pathway activation stimulates platelet-derived microparticles in hyperglycemic type 2 diabetes. Cardiovasc. Diabetol. 20, 77 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Joshi, M. B. et al. High glucose modulates IL-6 mediated immune homeostasis through impeding neutrophil extracellular trap formation. FEBS Lett. 587, 2241–2246 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Yadav, J. P. et al. Insights into the mechanisms of diabetic wounds: pathophysiology, molecular targets, and treatment strategies through conventional and alternative therapies. Inflammopharmacology 32, 149–228 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Rayman, G. et al. Guidelines on use of interventions to enhance healing of chronic foot ulcers in diabetes (IWGDF 2019 update). Diabetes Metab. Res. Rev. 36(Suppl 1), e3283 (2020).

    Article 
    PubMed 

    Google Scholar 

  • Guo, Y. et al. Multifunctional PtCuTe nanosheets with strong ROS scavenging and ROS-independent antibacterial properties promote diabetic wound healing. Adv. Mater. Deerfield Beach Fla 36, e2306292 (2024).

    Article 

    Google Scholar 

  • Wang, H., Xu, Z., Zhao, M., Liu, G. & Wu, J. Advances of hydrogel dressings in diabetic wounds. Biomater. Sci. 9, 1530–1546 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Schmidt, S., Moser, M. & Sperandio, M. The molecular basis of leukocyte recruitment and its deficiencies. Mol. Immunol. 55, 49–58 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zerbe, C. S. & Holland, S. M. Functional neutrophil disorders: chronic granulomatous disease and beyond. Immunol. Rev. 322, 71–80 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Fekadu, J., Modlich, U., Bader, P. & Bakhtiar, S. Understanding the role of LFA-1 in leukocyte adhesion deficiency type I (LAD I): moving towards inflammation? Int. J. Mol. Sci. 23, 3578 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Roos, D. et al. Hematologically important mutations: Leukocyte adhesion deficiency (second update). Blood Cells Mol. Dis. 99, 102726 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hanna, S. & Etzioni, A. Leukocyte adhesion deficiencies. Ann. N. Y. Acad. Sci. 1250, 50–55 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kuijpers, T. W. et al. Natural history and early diagnosis of LAD-1/variant syndrome. Blood 109, 3529–3537 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Skokowa, J., Dale, D. C., Touw, I. P., Zeidler, C. & Welte, K. Severe congenital neutropenias. Nat. Rev. Dis. Prim. 3, 17032 (2017).

    Article 
    PubMed 

    Google Scholar 

  • Welte, K., Zeidler, C. & Dale, D. C. Severe congenital neutropenia. Semin. Hematol. 43, 189–195 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Skokowa, J., Germeshausen, M., Zeidler, C. & Welte, K. Severe congenital neutropenia: inheritance and pathophysiology. Curr. Opin. Hematol. 14, 22–28 (2007).

    Article 
    PubMed 

    Google Scholar 

  • Mauch, P. et al. Hematopoietic stem cell compartment: acute and late effects of radiation therapy and chemotherapy. Int. J. Radiat. Oncol. Biol. Phys. 31, 1319–1339 (1995).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Lambertini, M., Ferreira, A. R., Del Mastro, L., Danesi, R. & Pronzato, P. Pegfilgrastim for the prevention of chemotherapy-induced febrile neutropenia in patients with solid tumors. Expert Opin. Biol. Ther. 15, 1799–1817 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Matsumura, R. et al. Successful bone marrow transplantation in a patient with acute myeloid leukemia developed from severe congenital neutropenia using modified chemotherapy and conditioning regimen for leukemia. Hematol. Rep. 16, 98–105 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Martínez-Alemán, S. R. et al. Understanding the entanglement: neutrophil extracellular traps (NETs) in cystic fibrosis. Front. Cell. Infect. Microbiol. 7, 104 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, G. & Nauseef, W. M. Neutrophil dysfunction in the pathogenesis of cystic fibrosis. Blood 139, 2622–2631 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Voynow, J. A. & Shinbashi, M. Neutrophil elastase and chronic lung disease. Biomolecules 11, 1065 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sly, P. D. et al. Risk factors for bronchiectasis in children with cystic fibrosis. N. Engl. J. Med. 368, 1963–1970 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Dickerhof, N. et al. Oxidative stress in early cystic fibrosis lung disease is exacerbated by airway glutathione deficiency. Free Radic. Biol. Med. 113, 236–243 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Prandini, P. et al. Transient receptor potential ankyrin 1 channels modulate inflammatory response in respiratory cells from patients with cystic fibrosis. Am. J. Respir. Cell Mol. Biol. 55, 645–656 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Yang, C. & Montgomery, M. Dornase alfa for cystic fibrosis. Cochrane Database Syst. Rev. 3, CD001127 (2021).

    PubMed 

    Google Scholar 

  • Smith, S., Rowbotham, N. J. & Charbek, E. Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis. Cochrane Database Syst. Rev. 8, CD008319 (2022).

    PubMed 

    Google Scholar 

  • Smith, S., Rowbotham, N. J. & Edwards, C. T. Short-acting inhaled bronchodilators for cystic fibrosis. Cochrane Database Syst. Rev. 6, CD013666 (2022).

    PubMed 

    Google Scholar 

  • Heinz, K. D., Walsh, A., Southern, K. W., Johnstone, Z. & Regan, K. H. Exercise versus airway clearance techniques for people with cystic fibrosis. Cochrane Database Syst. Rev. 6, CD013285 (2022).

    PubMed 

    Google Scholar 

  • Taylor-Cousar, J. L., Robinson, P. D., Shteinberg, M. & Downey, D. G. CFTR modulator therapy: transforming the landscape of clinical care in cystic fibrosis. Lancet Lond. Engl. 402, 1171–1184 (2023).

    Article 
    CAS 

    Google Scholar 

  • Bear, C. E. A therapy for most with cystic fibrosis. Cell 180, 211 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sergeev, V. et al. The extrapulmonary effects of cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis. Ann. Am. Thorac. Soc. 17, 147–154 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Nunoi, H., Nakamura, H., Nishimura, T. & Matsukura, M. Recent topics and advanced therapies in chronic granulomatous disease. Hum. Cell 36, 515–527 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • CA, J. et al. Hypergammaglobulinernia associated with severe, recurrent and chronic non-specific infection. Am. J. Child 88, 388–392 (1954).

  • Papayannopoulos, V. Neutrophil extracellular traps in immunity and disease. Nat. Rev. Immunol. 18, 134–147 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sharma, A. et al. Tamoxifen restores extracellular trap formation in neutrophils from patients with chronic granulomatous disease in a reactive oxygen species-independent manner. J. Allergy Clin. Immunol. 144, 597–600.e3 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Marsh, R. A. et al. Chronic granulomatous disease-associated IBD resolves and does not adversely impact survival following allogeneic HCT. J. Clin. Immunol. 39, 653–667 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bengtsson, A. A. & Rönnblom, L. Systemic lupus erythematosus: still a challenge for physicians. J. Intern. Med. 281, 52–64 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Tobin, R. et al. Atherosclerosis in systemic lupus erythematosus. Curr. Atheroscler. Rep. 25, 819–827 (2023).

    Article 
    PubMed 

    Google Scholar 

  • Rajagopalan, S. et al. Endothelial cell apoptosis in systemic lupus erythematosus: a common pathway for abnormal vascular function and thrombosis propensity. Blood 103, 3677–3683 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Lande, R. et al. Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus. Sci. Transl. Med. 3, 73ra19 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Villanueva, E. et al. Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus. J. Immunol. Baltim. Md 1950 187, 538–552 (2011).

    CAS 

    Google Scholar 

  • Scapini, P., Marini, O., Tecchio, C. & Cassatella, M. A. Human neutrophils in the saga of cellular heterogeneity: insights and open questions. Immunol. Rev. 273, 48–60 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Denny, M. F. et al. A distinct subset of proinflammatory neutrophils isolated from patients with systemic lupus erythematosus induces vascular damage and synthesizes type I IFNs. J. Immunol. Baltim. Md 1950 184, 3284–3297 (2010).

    CAS 

    Google Scholar 

  • Wang, L., Luqmani, R. & Udalova, I. A. The role of neutrophils in rheumatic disease-associated vascular inflammation. Nat. Rev. Rheumatol. 18, 158–170 (2022).

    Article 
    PubMed 

    Google Scholar 

  • Finckh, A. et al. Global epidemiology of rheumatoid arthritis. Nat. Rev. Rheumatol. 18, 591–602 (2022).

    PubMed 

    Google Scholar 

  • Birkelund, S. et al. Proteomic analysis of synovial fluid from rheumatic arthritis and spondyloarthritis patients. Clin. Proteom. 17, 29 (2020).

    Article 
    CAS 

    Google Scholar 

  • O’Neil, L. J. & Kaplan, M. J. Neutrophils in rheumatoid arthritis: breaking immune tolerance and fueling disease. Trends Mol. Med. 25, 215–227 (2019).

    Article 
    PubMed 

    Google Scholar 

  • McInnes, I. B. & Schett, G. The pathogenesis of rheumatoid arthritis. N. Engl. J. Med. 365, 2205–2219 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zhou, Y. et al. Spontaneous secretion of the citrullination enzyme PAD2 and cell surface exposure of PAD4 by neutrophils. Front. Immunol. 8, 1200 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Khandpur, R. et al. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Sci. Transl. Med. 5, 178ra40 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Carmona-Rivera, C. et al. Synovial fibroblast-neutrophil interactions promote pathogenic adaptive immunity in rheumatoid arthritis. Sci. Immunol. 2, eaag3358 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Delidakis, G., Kim, J. E., George, K. & Georgiou, G. Improving antibody therapeutics by manipulating the Fc domain: immunological and structural considerations. Annu. Rev. Biomed. Eng. 24, 249–274 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lefrançais, E. et al. IL-33 is processed into mature bioactive forms by neutrophil elastase and cathepsin G. Proc. Natl. Acad. Sci. USA 109, 1673–1678 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Raptis, S. Z., Shapiro, S. D., Simmons, P. M., Cheng, A. M. & Pham, C. T. N. Serine protease cathepsin G regulates adhesion-dependent neutrophil effector functions by modulating integrin clustering. Immunity 22, 679–691 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Grillet, B. et al. Matrix metalloproteinases in arthritis: towards precision medicine. Nat. Rev. Rheumatol. 19, 363–377 (2023).

    Article 
    PubMed 

    Google Scholar 

  • Glennon-Alty, L., Hackett, A. P., Chapman, E. A. & Wright, H. L. Neutrophils and redox stress in the pathogenesis of autoimmune disease. Free Radic. Biol. Med. 125, 25–35 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Eken, C. et al. Polymorphonuclear neutrophil-derived ectosomes interfere with the maturation of monocyte-derived dendritic cells. J. Immunol. Baltim. Md 1950 180, 817–824 (2008).

    CAS 

    Google Scholar 

  • Graham, D. B. & Xavier, R. J. Pathway paradigms revealed from the genetics of inflammatory bowel disease. Nature 578, 527–539 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Drury, B., Hardisty, G., Gray, R. D. & Ho, G.-T. Neutrophil extracellular traps in inflammatory bowel disease: pathogenic mechanisms and clinical translation. Cell. Mol. Gastroenterol. Hepatol. 12, 321–333 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Danne, C. Neutrophils: Old cells in IBD, new actors in interactions with the gut microbiota. Clin. Transl. Med. 14, e1739 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Magro, F. et al. European consensus on the histopathology of inflammatory bowel disease. J. Crohns Colitis 7, 827–851 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Swaminathan, A. et al. Faecal myeloperoxidase as a biomarker of endoscopic activity in inflammatory bowel disease. J. Crohns Colitis 16, 1862–1873 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mortha, A. et al. Neutralizing anti-granulocyte macrophage-colony stimulating factor autoantibodies recognize post-translational glycosylations on granulocyte macrophage-colony stimulating factor years before diagnosis and predict complicated Crohn’s disease. Gastroenterology 163, 659–670 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Danne, C., Skerniskyte, J., Marteyn, B. & Sokol, H. Neutrophils: from IBD to the gut microbiota. Nat. Rev. Gastroenterol. Hepatol. 21, 184–197 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Danne, C. et al. CARD9 in neutrophils protects from colitis and controls mitochondrial metabolism and cell survival. Gut 72, 1081–1092 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Han, X. et al. Loss of GM-CSF signalling in non-haematopoietic cells increases NSAID ileal injury. Gut 59, 1066–1078 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Gierlikowska, B., Stachura, A., Gierlikowski, W. & Demkow, U. Phagocytosis, degranulation and extracellular traps release by neutrophils-the current knowledge, pharmacological modulation and future prospects. Front. Pharmacol. 12, 666732 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Shen, F. et al. Fosfomycin enhances phagocyte-mediated killing of Staphylococcus aureus by extracellular traps and reactive oxygen species. Sci. Rep. 6, 19262 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cuffini, A. M. et al. The erythromycin-resistance in S. pyogenes does not limit the human polymorphonuclear cell antimicrobial activity. Int. J. Immunopathol. Pharmacol. 22, 239–242 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sharma, U. et al. Immunomodulatory active compounds from Tinospora cordifolia. J. Ethnopharmacol. 141, 918–926 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bystrzycka, W. et al. The effect of clindamycin and amoxicillin on neutrophil extracellular trap (NET) release. Cent. -Eur. J. Immunol. 41, 1–5 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Arampatzioglou, A. et al. Clarithromycin enhances the antibacterial activity and wound healing capacity in type 2 diabetes mellitus by increasing LL-37 load on neutrophil extracellular traps. Front. Immunol. 9, 2064 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jerjomiceva, N. et al. Enrofloxacin enhances the formation of neutrophil extracellular traps in bovine granulocytes. J. Innate Immun. 6, 706–712 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Reshetnikov, V. et al. Chemical tools for targeted amplification of reactive oxygen species in neutrophils. Front. Immunol. 9, 1827 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Morstyn, G., Foote, M., Perkins, D. & Vincent, M. The clinical utility of granulocyte colony-stimulating factor: early achievements and future promise. Stem Cells Dayt. Ohio 12, 213–227 (1994).

    Article 

    Google Scholar 

  • Welte, K. G-CSF: filgrastim, lenograstim and biosimilars. Expert Opin. Biol. Ther. 14, 983–993 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Pinto, L. et al. Comparison of pegfilgrastim with filgrastim on febrile neutropenia, grade IV neutropenia and bone pain: a meta-analysis of randomized controlled trials. Curr. Med. Res. Opin. 23, 2283–2295 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kourlaba, G. et al. Comparison of filgrastim and pegfilgrastim to prevent neutropenia and maintain dose intensity of adjuvant chemotherapy in patients with breast cancer. Support. Care Cancer J. Multinatl. Assoc. Support. Care Cancer 23, 2045–2051 (2015).

    Article 

    Google Scholar 

  • Kubo, K. et al. A randomized, double-blind trial of pegfilgrastim versus filgrastim for the management of neutropenia during CHASE(R) chemotherapy for malignant lymphoma. Br. J. Haematol. 174, 563–570 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Blair, H. A. & Scott, L. J. Tbo-filgrastim: a review in neutropenic conditions. BioDrugs Clin. Immunother. Biopharm. Gene Ther. 30, 153–160 (2016).

    Google Scholar 

  • Takano, T. et al. Efficacy and safety of pegfilgrastim biosimilar MD-110 in patients with breast cancer receiving chemotherapy: Single-arm phase III. Cancer Med. 12, 20242–20250 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Shi, Y. et al. 441P The prophylactic efficacy of telpegfilgrastim, a Y-shape branched pegylated G-CSF in patient with chemotherapy-induced neutropenia: A multicenter, randomized phase III study. Ann. Oncol. 34, S1635 (2023).

    Article 

    Google Scholar 

  • Bunney, T. D. & Katan, M. Targeting G-CSF to treat autoinflammation. Nat. Immunol. 24, 736–737 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Gabrilove, J. L. et al. Phase I study of granulocyte colony-stimulating factor in patients with transitional cell carcinoma of the urothelium. J. Clin. Invest. 82, 1454–1461 (1988).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Morstyn, G. et al. Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy. Lancet Lond. Engl. 1, 667–672 (1988).

    Article 
    CAS 

    Google Scholar 

  • Trillet-Lenoir, V. et al. Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. Eur. J. Cancer Oxf. Engl. 1990 29A, 319–324 (1993).

    CAS 

    Google Scholar 

  • Crawford, J. et al. Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N. Engl. J. Med. 325, 164–170 (1991).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Lord, B. I. et al. The kinetics of human granulopoiesis following treatment with granulocyte colony-stimulating factor in vivo. Proc. Natl. Acad. Sci. USA 86, 9499–9503 (1989).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Demetri, G. D. & Griffin, J. D. Granulocyte colony-stimulating factor and its receptor. Blood 78, 2791–2808 (1991).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Smith, T. J. et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J. Clin. Oncol. J. Am. Soc. Clin. Oncol. 24, 3187–3205 (2006).

    Article 
    CAS 

    Google Scholar 

  • Aapro, M. S. et al. EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours. Eur. J. Cancer Oxf. Engl. 1990 42, 2433–2453 (2006).

    CAS 

    Google Scholar 

  • Pettengell, R. et al. Neutropenia occurrence and predictors of reduced chemotherapy delivery: results from the INC-EU prospective observational European neutropenia study. Support. Care Cancer J. Multinatl. Assoc. Support. Care Cancer 16, 1299–1309 (2008).

    Article 

    Google Scholar 

  • Kuderer, N. M., Dale, D. C., Crawford, J. & Lyman, G. H. Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review. J. Clin. Oncol. J. Am. Soc. Clin. Oncol. 25, 3158–3167 (2007).

    Article 
    CAS 

    Google Scholar 

  • Renwick, W., Pettengell, R. & Green, M. Use of filgrastim and pegfilgrastim to support delivery of chemotherapy: twenty years of clinical experience. BioDrugs Clin. Immunother. Biopharm. Gene Ther. 23, 175–186 (2009).

    CAS 

    Google Scholar 

  • Kojima, S., Fukuda, M., Miyajima, Y., Matsuyama, T. & Horibe, K. Treatment of aplastic anemia in children with recombinant human granulocyte colony-stimulating factor. Blood 77, 937–941 (1991).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Toyama, K. et al. Clinical study of rhG-CSF (KRN8601) in patients with myelodysplastic syndrome. Rinsho Ketsueki 31, 937–945 (1990).

    CAS 
    PubMed 

    Google Scholar 

  • Link, H. Current state and future opportunities in granulocyte colony-stimulating factor (G-CSF). Support. Care Cancer J. Multinatl. Assoc. Support. Care Cancer 30, 7067–7077 (2022).

    Article 

    Google Scholar 

  • Dale, D. C. et al. A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia. Blood 81, 2496–2502 (1993).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Schmitt, M. et al. Biosimilar G-CSF based mobilization of peripheral blood hematopoietic stem cells for autologous and allogeneic stem cell transplantation. Theranostics 4, 280–289 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ringdén, O. et al. Treatment with granulocyte colony-stimulating factor after allogeneic bone marrow transplantation for acute leukemia increases the risk of graft-versus-host disease and death: a study from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. J. Clin. Oncol. J. Am. Soc. Clin. Oncol. 22, 416–423 (2004).

    Article 

    Google Scholar 

  • De Clercq, E. The bicyclam AMD3100 story. Nat. Rev. Drug Discov. 2, 581–587 (2003).

    Article 
    PubMed 

    Google Scholar 

  • Woollard, S. M. & Kanmogne, G. D. Maraviroc: a review of its use in HIV infection and beyond. Drug Des. Devel. Ther. 9, 5447–5468 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Grande, F., Giancotti, G., Ioele, G., Occhiuzzi, M. A. & Garofalo, A. An update on small molecules targeting CXCR4 as starting points for the development of anti-cancer therapeutics. Eur. J. Med. Chem. 139, 519–530 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • De Clercq, E. AMD3100/CXCR4 inhibitor. Front. Immunol. 6, 276 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • De Clercq, E. The AMD3100 story: the path to the discovery of a stem cell mobilizer (Mozobil). Biochem. Pharmacol. 77, 1655–1664 (2009).

    Article 
    PubMed 

    Google Scholar 

  • Hendrix, C. W. et al. Pharmacokinetics and safety of AMD-3100, a novel antagonist of the CXCR-4 chemokine receptor, in human volunteers. Antimicrob. Agents Chemother. 44, 1667–1673 (2000).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Liles, W. C. et al. Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood 102, 2728–2730 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Liles, W. C. et al. Augmented mobilization and collection of CD34+ hematopoietic cells from normal human volunteers stimulated with granulocyte-colony-stimulating factor by single-dose administration of AMD3100, a CXCR4 antagonist. Transfusion (Paris) 45, 295–300 (2005).

    Article 
    CAS 

    Google Scholar 

  • Eid, K. A., de, B., Miranda, E. C. M. & Aguiar, S. D. S. Mobilization and collection of CD34(+) cells for autologous transplantation of peripheral blood hematopoietic progenitor cells in children: analysis of two different granulocyte-colony stimulating factor doses. Rev. Bras. Hematol. E Hemoter. 37, 160–166 (2015).

    Article 

    Google Scholar 

  • Reddy, G. K., Crawford, J. & Jain, V. K. The role of plerixafor (AMD3100) in mobilizing hematopoietic progenitor cells in patients with hematologic malignancies. Support. Cancer Ther. 3, 73–76 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Brave, M. et al. FDA review summary: mozobil in combination with granulocyte colony-stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation. Oncology 78, 282–288 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • McDermott, D. H. et al. Plerixafor for the treatment of WHIM syndrome. N. Engl. J. Med. 380, 163–170 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Pillay, J. et al. Effect of the CXCR4 antagonist plerixafor on endogenous neutrophil dynamics in the bone marrow, lung and spleen. J. Leukoc. Biol. 107, 1175–1185 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wang, J., Tannous, B. A., Poznansky, M. C. & Chen, H. CXCR4 antagonist AMD3100 (plerixafor): from an impurity to a therapeutic agent. Pharmacol. Res. 159, 105010 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Lecavalier-Barsoum, M. et al. Targeting the CXCL12/CXCR4 pathway and myeloid cells to improve radiation treatment of locally advanced cervical cancer. Int. J. Cancer 143, 1017–1028 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Saur, D. et al. CXCR4 expression increases liver and lung metastasis in a mouse model of pancreatic cancer. Gastroenterology 129, 1237–1250 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Figueras, A. et al. A role for CXCR4 in peritoneal and hematogenous ovarian cancer dissemination. Mol. Cancer Ther. 17, 532–543 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Li, T. et al. The expression of CXCR4, CXCL12 and CXCR7 in malignant pleural mesothelioma. J. Pathol. 223, 519–530 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jang, Y.-G., Go, R.-E., Hwang, K.-A. & Choi, K.-C. Resveratrol inhibits DHT-induced progression of prostate cancer cell line through interfering with the AR and CXCR4 pathway. J. Steroid Biochem. Mol. Biol. 192, 105406 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Liu, H., Liu, Y., Liu, W., Zhang, W. & Xu, J. Author Correction: EZH2-mediated loss of miR-622 determines CXCR4 activation in hepatocellular carcinoma. Nat. Commun. 12, 6487 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Pan, H. et al. Forkhead box C1 boosts triple-negative breast cancer metastasis through activating the transcription of chemokine receptor-4. Cancer Sci. 109, 3794–3804 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Scala, S. et al. Human melanoma metastases express functional CXCR4. Clin. Cancer Res. J. Am. Assoc. Cancer Res. 12, 2427–2433 (2006).

    Article 
    CAS 

    Google Scholar 

  • Righi, E. et al. CXCL12/CXCR4 blockade induces multimodal antitumor effects that prolong survival in an immunocompetent mouse model of ovarian cancer. Cancer Res 71, 5522–5534 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Li, B. et al. AMD3100 augments the efficacy of mesothelin-targeted, immune-activating VIC-008 in mesothelioma by modulating intratumoral immunosuppression. Cancer Immunol. Res. 6, 539–551 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zeng, Y. et al. Dual blockade of CXCL12-CXCR4 and PD-1-PD-L1 pathways prolongs survival of ovarian tumor-bearing mice by prevention of immunosuppression in the tumor microenvironment. FASEB J. Publ. Fed. Am. Soc. Exp. Biol. 33, 6596–6608 (2019).

    CAS 

    Google Scholar 

  • Crees, Z. D. et al. Hematopoietic stem cell mobilization for allogeneic stem cell transplantation by motixafortide, a novel CXCR4 inhibitor. Blood Adv. 7, 5210–5214 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hoy, S. M. Motixafortide: first approval. Drugs 83, 1635–1643 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Mullard, A. CXCR4 chemokine antagonist scores a first FDA approval for WHIM syndrome. Nat. Rev. Drug Discov. 23, 411 (2024).

    PubMed 

    Google Scholar 

  • Geier, C. B. Mavorixafor: a new hope for WHIM syndrome. Blood 144, 1–2 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Badolato, R. et al. A phase 3 randomized trial of mavorixafor, a CXCR4 antagonist, for WHIM syndrome. Blood 144, 35–45 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Broderick, L. & Hoffman, H. M. IL-1 and autoinflammatory disease: biology, pathogenesis and therapeutic targeting. Nat. Rev. Rheumatol. 18, 448–463 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • An, E. An EUA for anakinra (Kineret) for COVID-19. Med Lett Drugs Ther 64, e203–e204 (2022).

  • Kenney-Jung, D. L. et al. Febrile infection-related epilepsy syndrome treated with anakinra. Ann. Neurol. 80, 939–945 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lai, Y.-C. et al. Anakinra usage in febrile infection related epilepsy syndrome: an international cohort. Ann. Clin. Transl. Neurol. 7, 2467–2474 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, T. K. M. & Klein, A. L. Rilonacept (Interleukin-1 Inhibition) for the treatment of pericarditis. Curr. Cardiol. Rep. 24, 23–30 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Imazio, M. et al. Sustained pericarditis recurrence risk reduction with long-term rilonacept. J. Am. Heart Assoc. 13, e032516 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Garbers, C., Heink, S., Korn, T. & Rose-John, S. Interleukin-6: designing specific therapeutics for a complex cytokine. Nat. Rev. Drug Discov. 17, 395–412 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Orders, M. An EUA for Tocilizumab (Actemra) for COVID-19. Med. Lett. Drugs Ther. 63, 113–114 (2021).

    Google Scholar 

  • Kleiter, I. & Gold, R. Present and future therapies in neuromyelitis optica spectrum disorders. Neurother. J. Am. Soc. Exp. Neurother. 13, 70–83 (2016).

    CAS 

    Google Scholar 

  • Zhang, C. et al. Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial. Lancet Neurol. 19, 391–401 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rose-John, S., Jenkins, B. J., Garbers, C., Moll, J. M. & Scheller, J. Targeting IL-6 trans-signalling: past, present and future prospects. Nat. Rev. Immunol. 23, 666–681 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Dwyer, M. P. et al. Discovery of 2-hydroxy-N, N-dimethyl-3-2-[[(R)-1-(5-methylfuran-2-yl) propyl] amino]-3, 4-dioxocyclobut-1-enylamino benzamide (SCH 527123): a potent, orally bioavailable CXCR2/CXCR1 receptor antagonist. J. Med. Chem. 49, 7603–7606 (2006).

  • Nair, P. et al. Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils: a randomized, placebo-controlled clinical trial. Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol. 42, 1097–1103 (2012).

    Article 
    CAS 

    Google Scholar 

  • Varney, M. L. et al. Small molecule antagonists for CXCR2 and CXCR1 inhibit human colon cancer liver metastases. Cancer Lett. 300, 180–188 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Singh, S. et al. Small-molecule antagonists for CXCR2 and CXCR1 inhibit human melanoma growth by decreasing tumor cell proliferation, survival, and angiogenesis. Clin. Cancer Res. 15, 2380–2386 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lazennec, G., Rajarathnam, K. & Richmond, A. CXCR2 chemokine receptor—a master regulator in cancer and physiology. Trends Mol. Med. 30, 37–55 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • McLornan, D. P., Pope, J. E., Gotlib, J. & Harrison, C. N. Current and future status of JAK inhibitors. Lancet Lond. Engl. 398, 803–816 (2021).

    Article 

    Google Scholar 

  • Almasi, S. et al. Effect of tofacitinib on clinical and laboratory findings in severe and resistant patients with COVID-19. Int. Immunopharmacol. 122, 110565 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Guimarães, P. O. et al. Tofacitinib in patients hospitalized with COVID-19 pneumonia. N. Engl. J. Med. 385, 406–415 (2021).

    Article 
    PubMed 

    Google Scholar 

  • Bissonnette, R. et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br. J. Dermatol. 175, 902–911 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Liu, L. Y., Craiglow, B. G., Dai, F. & King, B. A. Tofacitinib for the treatment of severe alopecia areata and variants: a study of 90 patients. J. Am. Acad. Dermatol. 76, 22–28 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • van der Heijde, D. et al. Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study. Ann. Rheum. Dis. 76, 1340–1347 (2017).

    Article 
    PubMed 

    Google Scholar 

  • Curtis, J. R., Xie, F., Yun, H., Bernatsky, S. & Winthrop, K. L. Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis. Ann. Rheum. Dis. 75, 1843–1847 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Taylor, P. C. Clinical efficacy of launched JAK inhibitors in rheumatoid arthritis. Rheumatol. Oxf. Engl. 58, i17–i26 (2019).

    Article 
    CAS 

    Google Scholar 

  • Rubin, R. Baricitinib is first approved COVID-19 immunomodulatory treatment. JAMA 327, 2281 (2022).

    CAS 
    PubMed 

    Google Scholar 

  • Freitas, E., Guttman-Yassky, E. & Torres, T. Baricitinib for the treatment of alopecia areata. Drugs 83, 761–770 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gavegnano, C. et al. Baricitinib reverses HIV-associated neurocognitive disorders in a SCID mouse model and reservoir seeding in vitro. J. Neuroinflammation 16, 182 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Przepiorka, D. et al. FDA approval summary: ruxolitinib for treatment of steroid-refractory acute graft-versus-host disease. Oncologist 25, e328–e334 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ajayi, S. et al. Ruxolitinib. Recent Results Cancer Res. 212, 119–132 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Mohamed, M.-E. F., Bhatnagar, S., Parmentier, J. M., Nakasato, P. & Wung, P. Upadacitinib: mechanism of action, clinical, and translational science. Clin. Transl. Sci. 17, e13688 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Nader, A. et al. Exposure-response analyses of upadacitinib efficacy and safety in phase II and III studies to support benefit-risk assessment in rheumatoid arthritis. Clin. Pharmacol. Ther. 107, 994–1003 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Dignass, A., Esters, P. & Flauaus, C. Upadacitinib in Crohn’s disease. Expert Opin. Pharmacother. 25, 359–370 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Markham, A. & Keam, S. J. Peficitinib: first global approval. Drugs 79, 887–891 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Talpaz, M. & Kiladjian, J.-J. Fedratinib, a newly approved treatment for patients with myeloproliferative neoplasm-associated myelofibrosis. Leukemia 35, 1–17 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Keam, S. J. Momelotinib: first approval. Drugs 83, 1709–1715 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Guo, R.-F. & Ward, P. A. Role of C5a in inflammatory responses. Annu. Rev. Immunol. 23, 821–852 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ghosh, M. & Rana, S. The anaphylatoxin C5a: structure, function, signaling, physiology, disease, and therapeutics. Int. Immunopharmacol. 118, 110081 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Khan, M. M. & Molony, D. A. In ANCA-associated vasculitis, avacopan was superior to prednisone taper for sustained remission. Ann. Intern. Med. 174, JC79 (2021).

    Article 
    PubMed 

    Google Scholar 

  • Jayne, D. R. W., Merkel, P. A., Schall, T. J., Bekker, P. & Advocate Study Group. Avacopan for the treatment of ANCA-associated vasculitis. N. Engl. J. Med. 384, 599–609 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Geetha, D. et al. Efficacy and safety of avacopan in patients with ANCA-associated vasculitis receiving rituximab in a randomised trial. Ann. Rheum. Dis. 83, 223–232 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Gomez-Arboledas, A. et al. C5aR1 antagonism alters microglial polarization and mitigates disease progression in a mouse model of Alzheimer’s disease. Acta Neuropathol. Commun. 10, 116 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lee, A. Avacopan: first approval. Drugs 82, 79–85 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • van Rhee, F. et al. Siltuximab for multicentric Castleman’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 15, 966–974 (2014).

    Article 
    PubMed 

    Google Scholar 

  • Schall, T. J. & Proudfoot, A. E. I. Overcoming hurdles in developing successful drugs targeting chemokine receptors. Nat. Rev. Immunol. 11, 355–363 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bilusic, M. et al. Phase I trial of HuMax-IL8 (BMS-986253), an anti-IL-8 monoclonal antibody, in patients with metastatic or unresectable solid tumors. J. Immunother. Cancer 7, 240 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gordon, M., Sinopoulou, V., Akobeng, A. K., Sarian, A. & Moran, G. W. Infliximab for maintenance of medically-induced remission in Crohn’s disease. Cochrane Database Syst. Rev. 2, CD012609 (2024).

    PubMed 

    Google Scholar 

  • Chen, J., Liao, J., Xiang, L., Zhang, S. & Yan, Y. Current knowledge of TNF-α monoclonal antibody infliximab in treating Kawasaki disease: a comprehensive review. Front. Immunol. 14, 1237670 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Schreiber, S. et al. Perspectives on subcutaneous infliximab for rheumatic diseases and inflammatory bowel disease: before, during, and after the COVID-19 era. Adv. Ther. 39, 2342–2364 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Brodsky, R. A. How I treat paroxysmal nocturnal hemoglobinuria. Blood 137, 1304–1309 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Paul, F. et al. International Delphi consensus on the management of AQP4-IgG+ NMOSD: recommendations for eculizumab, inebilizumab, and satralizumab. Neurol. Neuroimmunol. Neuroinflammation 10, e200124 (2023).

    Article 

    Google Scholar 

  • Harris, E. FDA approves vilobelimab for emergency use in hospitalized adults. JAMA 329, 1544 (2023).

    PubMed 

    Google Scholar 

  • Lu, J. D., Milakovic, M., Ortega-Loayza, A. G., Marzano, A. V. & Alavi, A. Pyoderma gangrenosum: proposed pathogenesis and current use of biologics with an emphasis on complement C5a inhibitor IFX-1. Expert Opin. Investig. Drugs 29, 1179–1185 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Giamarellos-Bourboulis, E. J. et al. Clinical efficacy of complement C5a inhibition by IFX-1 in hidradenitis suppurativa: an open-label single-arm trial in patients not eligible for adalimumab. Br. J. Dermatol. 183, 176–178 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Vu, T., Wiendl, H., Katsuno, M., Reddel, S. W. & Howard, J. F. Ravulizumab in myasthenia gravis: a review of the current evidence. Neuropsychiatr. Dis. Treat. 19, 2639–2655 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Begum, F., Khan, N., Boisclair, S., Malieckal, D. A. & Chitty, D. Complement inhibitors in the management of complement-mediated hemolytic uremic syndrome and paroxysmal nocturnal hemoglobinuria. Am. J. Ther. 30, e209–e219 (2023).

    Article 
    PubMed 

    Google Scholar 

  • Griffin, M. et al. Real-world experience of pegcetacoplan in paroxysmal nocturnal hemoglobinuria. Am. J. Hematol. (2024).

  • Sahebnasagh, A. et al. Neutrophil elastase inhibitor (sivelestat) may be a promising therapeutic option for management of acute lung injury/acute respiratory distress syndrome or disseminated intravascular coagulation in COVID-19. J. Clin. Pharm. Ther. 45, 1515–1519 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Matera, M. G., Rogliani, P., Ora, J., Calzetta, L. & Cazzola, M. A comprehensive overview of investigational elastase inhibitors for the treatment of acute respiratory distress syndrome. Expert Opin. Investig. Drugs 32, 793–802 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zeng, W., Song, Y., Wang, R., He, R. & Wang, T. Neutrophil elastase: from mechanisms to therapeutic potential. J. Pharm. Anal. 13, 355–366 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Churg, A. et al. Late intervention with a myeloperoxidase inhibitor stops progression of experimental chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 185, 34–43 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Lin, W., Chen, H., Chen, X. & Guo, C. The roles of neutrophil-derived myeloperoxidase (MPO) in diseases: the new progress. Antioxid. Basel Switz. 13, 132 (2024).

    Article 
    CAS 

    Google Scholar 

  • Holliday, Z. M. et al. Non-randomized trial of dornase alfa for acute respiratory distress syndrome secondary to COVID-19. Front. Immunol. 12, 714833 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Fisher, J. et al. Proteome profiling of recombinant DNAse therapy in reducing NETs and aiding recovery in COVID-19 patients. Mol. Cell. Proteom. MCP 20, 100113 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Chen, J. et al. DNA of neutrophil extracellular traps promote NF-κB-dependent autoimmunity via cGAS/TLR9 in chronic obstructive pulmonary disease. Signal Transduct. Target. Ther. 9, 163 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ray, A. L. et al. G-CSF is a novel mediator of T-cell suppression and an immunotherapeutic target for women with colon cancer. Clin. Cancer Res. J. Am. Assoc. Cancer Res. 29, 2158–2169 (2023).

    Article 
    CAS 

    Google Scholar 

  • Liu, L. et al. Cancer-associated adipocyte-derived G-CSF promotes breast cancer malignancy via Stat3 signaling. J. Mol. Cell Biol. 12, 723–737 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Coffelt, S. B. et al. IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature 522, 345–348 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Falchook, G. S. et al. A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors. Invest. N. Drugs 39, 1284–1297 (2021).

    Article 
    CAS 

    Google Scholar 

  • Weber, J. et al. 1040O Phase II trial of ipilimumab, nivolumab and tocilizumab for unresectable metastatic melanoma. Ann. Oncol. 32, S869 (2021).

    Article 

    Google Scholar 

  • Greene, S. et al. Inhibition of MDSC trafficking with SX-682, a CXCR1/2 inhibitor, enhances NK-cell immunotherapy in head and neck cancer models. Clin. Cancer Res. J. Am. Assoc. Cancer Res. 26, 1420–1431 (2020).

    Article 
    CAS 

    Google Scholar 

  • Kargl, J. et al. Neutrophil content predicts lymphocyte depletion and anti-PD1 treatment failure in NSCLC. JCI Insight 4, e130850 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, G. et al. Targeting YAP-dependent MDSC infiltration impairs tumor progression. Cancer Discov. 6, 80–95 (2016).

    Article 
    PubMed 

    Google Scholar 

  • Ortiz-Espinosa, S. et al. Complement C5a induces the formation of neutrophil extracellular traps by myeloid-derived suppressor cells to promote metastasis. Cancer Lett. 529, 70–84 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Corrales, L. et al. Anaphylatoxin C5a creates a favorable microenvironment for lung cancer progression. J. Immunol. Baltim. Md 1950 189, 4674–4683 (2012).

    CAS 

    Google Scholar 

  • Jung, K. et al. Targeting CXCR4-dependent immunosuppressive Ly6Clow monocytes improves antiangiogenic therapy in colorectal cancer. Proc. Natl. Acad. Sci. USA 114, 10455–10460 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bockorny, B. et al. BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial. Nat. Med. 26, 878–885 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Lu, X. et al. Effective combinatorial immunotherapy for castration-resistant prostate cancer. Nature 543, 728–732 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Proia, T. A. et al. STAT3 antisense oligonucleotide remodels the suppressive tumor microenvironment to enhance immune activation in combination with anti-PD-L1. Clin. Cancer Res. J. Am. Assoc. Cancer Res. 26, 6335–6349 (2020).

    Article 
    CAS 

    Google Scholar 

  • Yang, J. et al. WP1066, a small molecule inhibitor of STAT3, chemosensitizes paclitaxel-resistant ovarian cancer cells to paclitaxel by simultaneously inhibiting the activity of STAT3 and the interaction of STAT3 with Stathmin. Biochem. Pharmacol. 221, 116040 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Tsimberidou, A. M. et al. Phase 1 trial evaluating TTI-101, a first-in-class, orally bioavailable, small molecule, inhibitor of STAT3, in patients with advanced solid tumors. J. Clin. Oncol. 41, 3018 (2023).

    Article 

    Google Scholar 

  • Janjua, D. et al. Prognostic and therapeutic potential of STAT3: opportunities and challenges in targeting HPV-mediated cervical carcinogenesis. Crit. Rev. Oncol. Hematol. 197, 104346 (2024).

    Article 
    PubMed 

    Google Scholar 

  • Leonard, W. et al. Myeloid-derived suppressor cells reveal radioprotective properties through arginase-induced l-arginine depletion. Radiother. Oncol. J. Eur. Soc. Ther. Radiol. Oncol. 119, 291–299 (2016).

    Article 
    CAS 

    Google Scholar 

  • Cao, Y., Feng, Y., Zhang, Y., Zhu, X. & Jin, F. L-Arginine supplementation inhibits the growth of breast cancer by enhancing innate and adaptive immune responses mediated by suppression of MDSCs in vivo. BMC Cancer 16, 343 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Langarizadeh, M. A. et al. An overview of the history, current strategies, and potential future treatment approaches in erectile dysfunction: a comprehensive review. Sex. Med. Rev. 11, 253–267 (2023).

    Article 
    PubMed 

    Google Scholar 

  • Serafini, P. et al. Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J. Exp. Med. 203, 2691–2702 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Weed, D. T. et al. Tadalafil reduces myeloid-derived suppressor cells and regulatory T cells and promotes tumor immunity in patients with head and neck squamous cell carcinoma. Clin. Cancer Res. J. Am. Assoc. Cancer Res. 21, 39–48 (2015).

    Article 
    CAS 

    Google Scholar 

  • Weed, D. T. et al. The reversal of immune exclusion mediated by tadalafil and an anti-tumor vaccine also induces PDL1 upregulation in recurrent head and neck squamous cell carcinoma: interim analysis of a phase I clinical trial. Front. Immunol. 10, 1206 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chen, D. et al. Exenatide enhanced the antitumor efficacy on PD-1 blockade by the attenuation of neutrophil extracellular traps. Biochem. Biophys. Res. Commun. 619, 97–103 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kim, G. T. et al. Improving anticancer effect of aPD-L1 through lowering neutrophil infiltration by PLAG in tumor implanted with MB49 mouse urothelial carcinoma. BMC Cancer 22, 727 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tavazoie, M. F. et al. LXR/ApoE activation restricts innate immune suppression in cancer. Cell 172, 825–840.e18 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Behrens, L. M., van den Berg, T. K. & van Egmond, M. Targeting the CD47-SIRPα innate immune checkpoint to potentiate antibody therapy in cancer by neutrophils. Cancers 14, 3366 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Daver, N. et al. A phase 3, randomized, open-label study evaluating the safety and efficacy of magrolimab in combination with azacitidine in previously untreated patients with TP53-mutant acute myeloid leukemia. Blood 138, 3426 (2021).

    Article 

    Google Scholar 

  • Mehta, A. et al. Lemzoparlimab, a differentiated anti-cd47 antibody in combination with rituximab in relapsed and refractory non-Hodgkin’s lymphoma: initial clinical results. Blood 138, 3542 (2021).

    Article 

    Google Scholar 

  • Lopez-Beltran, A., Cookson, M. S., Guercio, B. J. & Cheng, L. Advances in diagnosis and treatment of bladder cancer. BMJ 384, e076743 (2024).

    Article 
    PubMed 

    Google Scholar 

  • Kemp, T. J. et al. Neutrophil stimulation with Mycobacterium bovis bacillus Calmette-Guerin (BCG) results in the release of functional soluble TRAIL/Apo-2L. Blood 106, 3474–3482 (2005).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Borges, V. M., Marinho, F. V., Caldeira, C. V. A., de Queiroz, N. M. G. P. & Oliveira, S. C. Bacillus Calmette-Guérin immunotherapy induces an efficient antitumor response to control murine melanoma depending on MyD88 signaling. Front. Immunol. 15, 1380069 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Da Gama Duarte, J. et al. Autoantibodies may predict immune-related toxicity: results from a phase I study of intralesional bacillus Calmette-Guérin followed by ipilimumab in patients with advanced metastatic melanoma. Front. Immunol. 9, 411 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mariathasan, S. et al. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature 554, 544–548 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tauriello, D. V. F. et al. TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis. Nature 554, 538–543 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Yamazaki, T. et al. Galunisertib plus neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: a single-arm, phase 2 trial. Lancet Oncol. 23, 1189–1200 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Formenti, S. C. et al. Focal irradiation and systemic TGFβ blockade in metastatic breast cancer. Clin. Cancer Res. J. Am. Assoc. Cancer Res. 24, 2493–2504 (2018).

    Article 
    CAS 

    Google Scholar 

  • Yoo, C. et al. Phase 2 trial of bintrafusp alfa as second-line therapy for patients with locally advanced/metastatic biliary tract cancers. Hepatol. Baltim. Md 78, 758–770 (2023).

    Google Scholar 

  • Linde, I. L. et al. Neutrophil-activating therapy for the treatment of cancer. Cancer Cell 41, 356–372.e10 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Fontes, J., Castellano-González, G., Macena, B. C. L. & Afonso, P. Hitchhiking to the abyss. Ecol. Evol. 13, e10126 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Shaw, I. et al. Advancements and prospects of lipid-based nanoparticles: dual frontiers in cancer treatment and vaccine development. J. Microencapsul. 41, 226–254 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wang, M. et al. Neutrophil hitchhiking: riding the drug delivery wave to treat diseases. Drug Dev. Res. 85, e22169 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Pan, J. et al. Bacteria-derived outer-membrane vesicles hitchhike neutrophils to enhance ischemic stroke therapy. Adv. Mater. Deerfield Beach Fla 35, e2301779 (2023).

    Article 

    Google Scholar 

  • Mu, Q. et al. Ligustrazine nanoparticle hitchhiking on neutrophils for enhanced therapy of cerebral ischemia-reperfusion injury. Adv. Sci. Weinh. Baden.-Wurtt. Ger. 10, e2301348 (2023).

    Google Scholar 

  • Luo, Z. et al. Neutrophil hitchhiking for drug delivery to the bone marrow. Nat. Nanotechnol. 18, 647–656 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Tang, X. et al. Natural cell based biomimetic cellular transformers for targeted therapy of digestive system cancer. Theranostics 12, 7080–7107 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cully, M. Exosome-based candidates move into the clinic. Nat. Rev. Drug Discov. 20, 6–7 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Thébaud, B. & Stewart, D. J. Exosomes: cell garbage can, therapeutic carrier, or trojan horse? Circulation 126, 2553–2555 (2012).

    Article 
    PubMed 

    Google Scholar 

  • Li, L. et al. Neutrophil-derived exosome from systemic sclerosis inhibits the proliferation and migration of endothelial cells. Biochem. Biophys. Res. Commun. 526, 334–340 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Yu, Y. et al. An injectable, activated neutrophil-derived exosome mimetics/extracellular matrix hybrid hydrogel with antibacterial activity and wound healing promotion effect for diabetic wound therapy. J. Nanobiotechnol. 21, 308 (2023).

    Article 
    CAS 

    Google Scholar 

  • Wang, J. et al. Inflammatory tumor microenvironment responsive neutrophil exosomes-based drug delivery system for targeted glioma therapy. Biomaterials 273, 120784 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Genschmer, K. R. et al. Activated PMN exosomes: pathogenic entities causing matrix destruction and disease in the lung. Cell 176, 113–126.e15 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Blanch-Ruiz, M. A., Ortega-Luna, R., Martínez-Cuesta, M. Á. & Álvarez, Á. The neutrophil secretome as a crucial link between inflammation and thrombosis. Int. J. Mol. Sci. 22, 4170 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, H., Zang, J., Zhao, Z., Zhang, Q. & Chen, S. The advances of neutrophil-derived effective drug delivery systems: a key review of managing tumors and inflammation. Int. J. Nanomed. 16, 7663–7681 (2021).

    Article 
    CAS 

    Google Scholar 

  • Clarke, S. J. et al. Use of inflammatory markers to guide cancer treatment. Clin. Pharmacol. Ther. 90, 475–478 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bhattacharya, S. & Munshi, C. Biological significance of C-reactive protein, the ancient acute phase functionary. Front. Immunol. 14, 1238411 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Demir, A. K. et al. The relationship between the neutrophil-lymphocyte ratio and disease activity in patients with ulcerative colitis. Kaohsiung J. Med. Sci. 31, 585–590 (2015).

    Article 
    PubMed 

    Google Scholar 

  • Liu, J. et al. Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage. J. Transl. Med. 18, 206 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Diakos, C. I., Charles, K. A., McMillan, D. C. & Clarke, S. J. Cancer-related inflammation and treatment effectiveness. Lancet Oncol. 15, e493–503 (2014).

    Article 
    PubMed 

    Google Scholar 

  • Gabrilovich, D. I., Ostrand-Rosenberg, S. & Bronte, V. Coordinated regulation of myeloid cells by tumours. Nat. Rev. Immunol. 12, 253–268 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Proctor, M. J. et al. A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer. Br. J. Cancer 107, 695–699 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chua, W., Charles, K. A., Baracos, V. E. & Clarke, S. J. Neutrophil/lymphocyte ratio predicts chemotherapy outcomes in patients with advanced colorectal cancer. Br. J. Cancer 104, 1288–1295 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhang, M. et al. G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery. Signal Transduct. Target. Ther. 9, 88 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Deng, Z. et al. TGF-β signaling in health, disease, and therapeutics. Signal Transduct. Target. Ther. 9, 61 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kalafati, L., Hatzioannou, A., Hajishengallis, G. & Chavakis, T. The role of neutrophils in trained immunity. Immunol. Rev. 314, 142–157 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Chen, M. & Wang, S. Preclinical development and clinical studies of targeted JAK/STAT combined Anti-PD-1/PD-L1 therapy. Int. Immunopharmacol. 130, 111717 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • de Oliveira, S., Rosowski, E. E. & Huttenlocher, A. Neutrophil migration in infection and wound repair: going forward in reverse. Nat. Rev. Immunol. 16, 378–391 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jung, E. H. et al. Mobilization of hematopoietic stem cells with lenograstim in multiple myeloma patients: Prospective multicenter observational study (KMM122). Cancer Med. 12, 9186–9193 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tanaka, H. et al. Three types of recombinant human granulocyte colony-stimulating factor have equivalent biological activities in monkeys. Cytokine 9, 360–369 (1997).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Gálffy, G. [Lipegfilgrastim – long acting G-CSF in prevention of chemotherapy-induced neutropenia]. Magy. Onkol. 62, 195–200 (2018).

  • link

    Leave a Reply

    Your email address will not be published. Required fields are marked *