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However, its clinical utility is constrained by low response rates and acquired resistance. Tumour\u2010associated neutrophils (TANs), key players in tumour immunoregulation, have emerged as critical mediators of ICB responsiveness and resistance, highlighting the therapeutic potential of combining TAN\u2010targeted strategies with immune checkpoint inhibitors (ICIs). This review systematically synthesizes current knowledge of neutrophils in ICB resistance from several dimensions: (1) clinical indicators of neutrophils, such as the neutrophil\u2010to\u2010lymphocyte ratio (NLR) and tissue TANs abundance, as predictors of ICI response and patients prognosis; (2) multifaceted TAN\u2010involved resistance mechanisms, including direct T cell inhibition, antigen presentation impairment, function modulation of other immune cells, promotion of tumour angiogenesis, and elevation of tumour mutation burden (TMB); (3) combination therapeutic strategies targeting TAN generation\/ exhaustion, recruitment, phenotypic polarization, activation, proangiogenic functions, and neutrophil extracellular traps (NETs), along with progress in related clinical trials. Combinatorial approaches integrating TAN\u2010targeted therapies with ICIs hold substantial promise for overcoming resistance by reshaping the immune microenvironment. Elucidating neutrophil\u2010mediated resistance mechanisms and optimizing combination strategies will pave the way for precision tumour immunotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>TANs drive ICI resistance via antitumour immune remodelling, angiogenesis promotion, and elevation of tumour mutation burden<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Neutrophil biomarkers (e.g., NLR, TAN abundance) show strong predictive value for ICI response and prognosis.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Targeting TAN recruitment, polarization, function and NETosis represents a promising strategy to overcome ICI resistance.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Numerous clinical trials are evaluating combination therapies targeting neutrophils to enhance immunotherapy efficacy.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70582","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T04:26:56Z","timestamp":1767673616000},"source":"Crossref","is-referenced-by-count":5,"title":["Targeting neutrophil\u2010driven immunosuppression: A strategy to overcome immune checkpoint inhibitor resistance"],"prefix":"10.1002","volume":"16","author":[{"given":"Ying","family":"Ning","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology The Affiliated Hospital of Qingdao University  Qingdao China"},{"name":"Center of Tumor Immunology and Cytotherapy Medical Research Center The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Lei","sequence":"additional","affiliation":[{"name":"Center of Tumor Immunology and Cytotherapy Medical Research Center The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The Affiliated Hospital of Qingdao University  Qingdao 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