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This review highlights tumour-associated neutrophils (TANs) as key mediators linking ICB responsiveness and failure, emphasizing TAN-targeted combination approaches with immune checkpoint inhibitors (ICIs). It synthesizes neutrophil clinical indicators, TAN-driven resistance mechanisms, and TAN-focused strategies including recruitment, polarization, functional modulation and NETosis, integrating evidence from related clinical trials to support precision immunotherapy.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/targeting-neutrophil-driven-immunosuppression-a-strategy-to-overcome-immune-checkpoint-inhibitor-resistance/444187/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/targeting-neutrophil-driven-immunosuppression-a-strategy-to-overcome-immune-checkpoint-inhibitor-resistance/444187.png","ImageObject",300,407,{"name":92,"@type":93},"Nguyễn Văn Học","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-06","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",14,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why does immune checkpoint blockade often fail in patients?","Question",{"text":113,"@type":114},"ICB can be limited by low response rates and acquired immune checkpoint inhibitor resistance, reducing durable therapeutic benefit.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What role do tumour-associated neutrophils play in ICI resistance?",{"text":118,"@type":114},"TANs help drive ICI resistance through antitumour immune remodelling, promotion of angiogenesis, and elevation of tumour mutation burden, while also influencing responsiveness.",{"name":120,"@type":111,"acceptedAnswer":121},"How can TAN-targeted strategies improve the effectiveness of ICIs?",{"text":122,"@type":114},"Combining ICIs with therapies that target TAN recruitment, polarization, function and NETosis may reshape the tumour immune microenvironment and overcome resistance. The review also summarizes ongoing clinical trials evaluating such combinations.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},444187,1790908197,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},1374402739827,"https://ap-avatar.wpscdn.com/avatar/14000c97e7351f1a627?x-image-process=image/resize,m_fixed,w_180,h_180&k=1787885694763230660","DOI: 10.1002/ctm2.70582  \nREVIEW  \nTargeting neutrophil-driven immunosuppression: A strategy to overcome immune checkpoint inhibitor resistance  \nYing Ning1,2  Ke Lei2  Xinyan Gao1  Yan Kong1  Yuping Shan1  Tian Tian1  Zhumei Cui1   He Ren2   \n1 Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, China  \n2 Center of Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, China  \nCorrespondence  \nHeRen, Center of Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China. [Email:](Email: herenrh@163.com)[ herenrh@163.com](Email: herenrh@163.com)  \nZhumei Cui and Tian Tian, Department of Obstetricsand Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.  \n[Email:](Email: cuizhumei1966@qdu.edu.cn)[ cuizhumei1966@qdu.edu.cn](Email: cuizhumei1966@qdu.edu.cn); [tiantian@qdu.edu.cn](tiantian@qdu.edu.cn)  \nGraphical Abstract  \n∙ TANs drive ICI resistance via antitumour immune remodelling, angiogenesis promotion, and elevation of tumour mutation burden  \n∙ Neutrophil biomarkers (e.g., NLR, TAN abundance) show strong predictive value for ICI response and prognosis.  \nClin. Transl. Med. 2026;16:e70582 .  \n[https://doi.org/10.1002/ctm2.70582](https://doi.org/10.1002/ctm2.70582)  \n[wileyonlinelibrary.com/journal/ctm2](wileyonlinelibrary.com/journal/ctm2)  \nNING et al.  \n∙ Targeting TAN recruitment, polarization, function and NETosis represents a promising strategy to overcome ICI resistance.  \n∙ Numerous clinical trials are evaluating combination therapies targeting neutrophils to enhance immunotherapy efficacy.  \nDOI: 10.1002/ctm2.70582  \nREVIEW  \nTargeting neutrophil-driven immunosuppression: A strategy to overcome immune checkpoint inhibitor resistance  \nYing Ning1,2  Ke Lei2  Xinyan Gao1  Yan Kong1  Yuping Shan1  Tian Tian1  Zhumei Cui1   He Ren2   \n1 Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, China  \n2 Center of Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, China  \nCorrespondence  \nHe Ren, Center of Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China. [Email:](Email: herenrh@163.com)[ herenrh@163.com](Email: herenrh@163.com)  \nZhumei Cui and Tian Tian, Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.  \nEmail: [cuizhumei1966@qdu.edu.cn](cuizhumei1966@qdu.edu.cn); [tiantian@qdu.edu.cn](tiantian@qdu.edu.cn)  \nFunding information  \nChina Postdoctoral Science Foundation, Grant/Award Number: 2025M772174; Shandong Postdoctoral Science Foundation, Grant/Award Number:  \nSDCX-ZG-202502052; Science Foundation for Young Scientists of the Affiliated Hospital of Qingdao University,  \nGrant/Award Number: QDFYQN2024118; National Natural Science Foundation of China, Grant/Award Number: 82472719; Qingdao Municipal Science and  \nAbstract  \nImmune checkpoint blockade (ICB) has revolutionized tumour therapy by relieving immunosuppression and restoring effector T cell cytotoxicity. However, its clinical utility is constrained by low response rates and acquired resistance. Tumour-associated neutrophils (TANs), key players in tumour immunoregulation, have emerged as critical mediators of ICB responsiveness and resistance, highlighting the therapeutic potential of combining TAN-targeted strategies with immune checkpoint inhibitors (ICIs) . This review systematically synthesizes current knowledge of neutrophils in ICB resistance from several dimensions:  \n(1) clinical indicators of neutrophils, such as the neutrophil-to-lymphocyte ratio (NLR) and tissue TANs abundance, as predictors of ICI response and patients prognosis; (2) multifaceted TAN-involved resistance mechanisms, including direct T cell inhi","cbCaijtNAMRMWC6D","https://ap.wps.com/l/cbCaijtNAMRMWC6D","pdf",2022748,31,"English","# Key points\n# Introduction\n# Clinical indicators of neutrophils in ICI response\n## Neutrophil-to-lymphocyte ratio (NLR) and tissue TAN abundance\n# TAN-driven mechanisms of ICI resistance\n## Direct T cell inhibition and antigen presentation impairment\n## Immune cell function modulation\n## Tumour angiogenesis and tumour mutation burden elevation\n# Combination therapeutic strategies targeting TANs\n## Generation/exhaustion and recruitment\n## Phenotypic polarization and activation\n## Proangiogenic functions and NETosis\n# Conclusion and future directions","[{\"question\":\"Why does immune checkpoint blockade often fail in patients?\",\"answer\":\"ICB can be limited by low response rates and acquired immune checkpoint inhibitor resistance, reducing durable therapeutic benefit.\"},{\"question\":\"What role do tumour-associated neutrophils play in ICI resistance?\",\"answer\":\"TANs help drive ICI resistance through antitumour immune remodelling, promotion of angiogenesis, and elevation of tumour mutation burden, while also influencing responsiveness.\"},{\"question\":\"How can TAN-targeted strategies improve the effectiveness of ICIs?\",\"answer\":\"Combining ICIs with therapies that target TAN recruitment, polarization, function and NETosis may reshape the tumour immune microenvironment and overcome resistance. The review also summarizes ongoing clinical trials evaluating such combinations.\"}]","Targeting neutrophil-driven immunosuppression - A strategy to overcome immune checkpoint inhibitor resistance | PDF",1790707147,78]