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PD-1 and PD-L ligands are central checkpoint molecules whose interaction restrains adaptive immunity by suppressing effector T-cell activity while promoting immunosuppressive regulatory T-cell (Treg) function, supporting immune homeostasis. Tumors co-opt the PD-1/PD-L1 axis to enable immune escape. Blocking PD-1/PD-L1 with neutralizing antibodies can restore T-cell function and strengthen antitumor immunity. This review summarizes PD-1/PD-L1 regulatory mechanisms in cancers and outlines progress in clinical studies targeting these pathways, including combined therapeutic strategies.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/regulatory-mechanisms-of-pd-1pd-l1-in-cancers/330651/",{"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/regulatory-mechanisms-of-pd-1pd-l1-in-cancers/330651.png","ImageObject",300,407,{"name":92,"@type":93},"Eliana","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What role does the PD-1/PD-L1 interaction play in immune regulation?","Question",{"text":113,"@type":114},"It negatively regulates adaptive immune responses by inhibiting effector T-cell activity and enhancing immunosuppressive regulatory T-cell (Treg) function, helping maintain immune homeostasis.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How do cancer cells use the PD-1/PD-L1 axis to promote immune escape?",{"text":118,"@type":114},"Cancer cells express PD-L1 or PD-L2 that bind PD-1 on T cells, delivering inhibitory signals that suppress T-cell activation and contribute to immune escape.",{"name":120,"@type":111,"acceptedAnswer":121},"Why is blockade of PD-1/PD-L1 considered effective in cancer therapy?",{"text":122,"@type":114},"Neutralizing antibodies targeting PD-1/PD-L1 restore T-cell activity and enhance antitumor immunity, showing notable success in cancer treatment.","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},330651,1789996473,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":39,"category_name":40,"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":31,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},4398048949847,"https://ap-avatar.wpscdn.com/avatar/400002536579ef2da7f?_k=1778318612642679267","Lin etal. Molecular Cancer (2024) 23:108 Molecular Cancer  \n[https://doi.org/10.1186/s12943-024-02023-w](https://doi.org/10.1186/s12943-024-02023-w)  \nREVIEW Open Access  \nRegulatory mechanisms of PD-1/PD-L1 in cancers  \nXin Lin 1,2,3,4, Kuan Kang 1,2,3,4, Pan Chen 1, Zhaoyang Zeng 1,2,3,4, Guiyuan Li 1,2,3,4, Wei Xiong 1,2,3,4, Mei Yi5* and Bo Xiang 1,2,3,4,6*  \nAbstract  \nImmune evasion contributes to cancer growth and progression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. The programmed death protein 1 (PD-1) and programmed cell death ligands (PD-Ls) are considered to be the major immune checkpoint molecules. The interaction of PD-1 and PD-L1 negatively regulates adaptive immune response mainly by inhibiting the activity of effector T cells while enhancing the function of immunosuppressive regulatory T cells (Tregs), largely contributing to the maintenance of immune homeostasis that prevents dysregulated immunity and harmful immune responses. However, cancer cells exploit the PD-1/PD-L1 axis to cause immune escape in cancer development and progression. Blockade of PD-1/PD-L1 by neutralizing antibodies restores T cells activity and enhances anti-tumor immunity, achieving remarkable success in cancer therapy. Therefore, the regulatory mechanisms of PD-1/PD-L1 in cancers have attracted an increasing attention. This article aims to provide a comprehensive review of the roles of the PD-1/PD-L1 signaling in human autoimmune diseases and cancers. We summarize all aspects of regulatory mechanisms underlying the expression and activity of PD-1 and PD-L1 in cancers, including genetic, epigenetic, post-transcriptional and post-translational regulatory mechanisms. In addition, we further summarize the progress in clinical research on the antitumor effects of targeting PD-1/PD-L1 antibodies alone and in combination with other therapeutic approaches, providing new strategies for finding new tumor markers and developing combined therapeutic approaches.  \nKeywords Tumor immunity, PD-1, PD-L1, Regulatory mechanism, Combination therapy  \n*Correspondence: Mei Yi [yi_mei@csu.edu.cn](yi_mei@csu.edu.cn)[ ](yi_mei@csu.edu.cn)Bo Xiang [xiangbol in@csu.edu.cn](xiangbol in@csu.edu.cn)  \n1NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China  \n2FuRong Laboratory, Changsha 410078, Hunan, China  \n3Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha 410008, Hunan, China  \n4The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University,  \nChangsha 410078, Hunan, China  \n5Department of Dermotology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China  \n6Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Tongzipo Road, Changsha 410013, Hunan, China  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http:/","cbCaiiKLe336RBMC","https://ap.wps.com/l/cbCaiiKLe336RBMC","pdf",4000007,"English","# Abstract\n# Introduction\n## PD-1 and PD-L1/PD-L2 biology and immune regulation\n## PD-1/PD-L1 interactions in cancer immune escape","[{\"question\":\"What role does the PD-1/PD-L1 interaction play in immune regulation?\",\"answer\":\"It negatively regulates adaptive immune responses by inhibiting effector T-cell activity and enhancing immunosuppressive regulatory T-cell (Treg) function, helping maintain immune homeostasis.\"},{\"question\":\"How do cancer cells use the PD-1/PD-L1 axis to promote immune escape?\",\"answer\":\"Cancer cells express PD-L1 or PD-L2 that bind PD-1 on T cells, delivering inhibitory signals that suppress T-cell activation and contribute to immune escape.\"},{\"question\":\"Why is blockade of PD-1/PD-L1 considered effective in cancer therapy?\",\"answer\":\"Neutralizing antibodies targeting PD-1/PD-L1 restore T-cell activity and enhance antitumor immunity, showing notable success in cancer treatment.\"}]","Regulatory mechanisms of PD-1/PD-L1 in cancers | PDF",1789989645,126]