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Chemotherapy can directly kill tumor cells and also trigger effective anti-tumor immune responses. Clinical approvals for first-line use of ICI-chemotherapy combinations, including PD-1/PD-L1 inhibitors, motivate this review, which analyzes mechanisms involving immunogenic cell death (ICD) and TME reprogramming through metabolic and microbiome remodeling.",{"@graph":69,"@context":122},[70,84,105],{"@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/the-application-basis-of-immuno-checkpoint-inhibitors-combined-with-chemotherapy-in-cancer-treatment/384399/",{"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/the-application-basis-of-immuno-checkpoint-inhibitors-combined-with-chemotherapy-in-cancer-treatment/384399.png","ImageObject",300,407,{"name":92,"@type":93},"dhado","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why do not all cancer patients benefit from immuno-checkpoint inhibitors (ICIs) monotherapy?","Question",{"text":112,"@type":113},"Because responses are shaped by a complex and heterogeneous tumor microenvironment (TME), which can promote inhibition of effective immune responses.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How can chemotherapy support anti-tumor immunity when combined with ICIs?",{"text":117,"@type":113},"Chemotherapy can directly kill tumor cells and also stimulate effective anti-tumor immune responses, thereby improving the overall efficacy of treatment.",{"name":119,"@type":110,"acceptedAnswer":120},"What mechanisms does the review emphasize for combined ICI and chemotherapy therapy?",{"text":121,"@type":113},"The review summarizes mechanisms related to immunogenic cell death (ICD) and TME reprogramming, particularly from perspectives of metabolic reprogramming and microbiome reprogramming.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},384399,1790413289,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},5909893218464,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","TYPE Mini Review  \nPUBLISHED 10 January 2023  \nDOI 10.3389/fimmu.2022.1088886  \nOPEN ACCESS  \nEDITED BY  \nJian Zhang,  \nSouthern Medical University, China  \nREVIEWED BY  \nJake ODonnell, The University of Queensland, Australia  \nDalil Hannani,  \nGrenoble (TIMC-IMAG), France Jian Qiao,  \nUniversity of Texas Southwestern Medical Center, United States  \n*CORRESPONDENCE  \nKe Wang  \n[wangke@fmmu.edu.cn](wangke@fmmu.edu.cn)[ ](wangke@fmmu.edu.cn)Zhi-Nan Chen  \n [znchen@fmmu.edu.cn](znchen@fmmu.edu.cn)  \n†These authors have contributed equally to this work  \nSPECIALTY SECTION  \nThis article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology  \nRECEIVED 03 November 2022  \nACCEPTED 20 December 2022  \nPUBLISHED 10 January 2023  \nCITATION  \nShi M-Y, Liu H-G, Chen X-H, Tian Y, Chen Z-N and Wang K (2023) The application basis of immunocheckpoint inhibitors combined with chemotherapy in cancer treatment. Front. Immunol. 13:1088886 .  \ndoi: 10.3389/fimmu.2022.1088886  \nCOPYRIGHT  \n© 2023 Shi, Liu, Chen, Tian, Chen and Wang. This is an open-access article distributed under the terms of the  \nCreative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nThe application basis of immuno-checkpoint inhibitors combined with chemotherapy in cancer treatment  \nMing-Yan Shi †, Han-Ge Liu †, Xiao-Hong Chen, Ye Tian, Zhi-Nan Chen* and Ke Wang*  \nNational Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China  \nImmuno-checkpoint inhibitors (ICIs) bring a promising prospect for patients with cancers, which restrains the growth of tumor cells by enhancing antitumor activity. Nevertheless, not all patients benefit from the administration of ICIs monotherapy. The partial response or resistance to ICIs is mainly due to the complex and heterogenous tumor microenvironment (TME) . The combined therapy is necessary for improving the efficacy of tumor treatment. Chemotherapy is reported not only to kill tumor cells directly, but also to stimulate effective anti-tumor immune responses. Several combined therapies of ICIs and chemotherapeutic agents have been approved for the first-line treatment of cancers, including PD-1/PD-L1 inhibitors. This review summarizes the potential mechanisms of the combined therapy of ICIs and chemotherapeutic agents in inducing immunogenic cell death (ICD) andreprogramming TME, and elucidates the possible anti-tumor effects of combined therapy from the perspective of metabolic reprogramming and microbiome reprogramming.  \nKEYWORDS  \nimmuno-checkpoint inhibitors, chemotherapy, tumor microenvironment, immunogenic cell death, anti-tumor activity  \nIntroduction  \nMalignant tumors, as a type of incurable diseases, have threatened human health seriously owing to the immunosuppressive tumor microenvironment. The tumor immunotherapies dramatically make a monumental breakthrough for cancer treatment and bring significant improvement for patient survival by boosting effective immune response to eliminate malignant cells (1, 2) . Oncolytic virus therapies, cancer vaccines, cytokine therapies, adoptive cell transfer therapies, and ICIs are included, and ICIs, which include inhibitors of the programmed cell death protein 1 (PD-1),  \nFrontiers in Immunology 01 [frontiersin.org](frontiersin.org)  \nprogrammed cell death-ligand 1 (PD-L1), and the cytotoxic T lymphocyte-associated protein 4 (CTLA-4), have been broadly used in clinical applications and contribute to prolonged survival for lung cancer patients (2–5) .  \nHowever, not all patients benefit from immune checkpoint blockade therapy (6, 7) . Based on response t","cbCaic07eaE2rO2p","https://ap.wps.com/l/cbCaic07eaE2rO2p","pdf",953847,"English","# Introduction\n## Limitations of ICI monotherapy and TME complexity\n## Patient response categories to immune checkpoint blockade\n## Role of immune cell infiltration and TME suppressors\n## Rationale for combining ICIs with chemotherapy\n## Clinical evidence and approvals of ICI-chemotherapy regimens","[{\"question\":\"Why do not all cancer patients benefit from immuno-checkpoint inhibitors (ICIs) monotherapy?\",\"answer\":\"Because responses are shaped by a complex and heterogeneous tumor microenvironment (TME), which can promote inhibition of effective immune responses.\"},{\"question\":\"How can chemotherapy support anti-tumor immunity when combined with ICIs?\",\"answer\":\"Chemotherapy can directly kill tumor cells and also stimulate effective anti-tumor immune responses, thereby improving the overall efficacy of treatment.\"},{\"question\":\"What mechanisms does the review emphasize for combined ICI and chemotherapy therapy?\",\"answer\":\"The review summarizes mechanisms related to immunogenic cell death (ICD) and TME reprogramming, particularly from perspectives of metabolic reprogramming and microbiome reprogramming.\"}]","The application basis of immuno-checkpoint inhibitors combined with chemotherapy in cancer treatment | PDF",1790263073,23]