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It explains why some cancers resist anti–PD-1/PD-L1 therapies, focusing on interferon-gamma–induced release of exoPD-L1 that suppresses anticancer immune responses and links to anti-PD-1 outcomes. The article covers mechanisms, regulation, exoPD-L1 as biomarkers, analytical methods for quantifying it, therapeutic strategies targeting it, and its roles beyond oncology.",{"@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":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/exosomal-pd-l1-in-cancer-and-other-fields-recent-advances-and-perspectives/332049/",{"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/exosomal-pd-l1-in-cancer-and-other-fields-recent-advances-and-perspectives/332049.png","ImageObject",300,407,{"name":92,"@type":93},"Aurora","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the significance of PD-1/PD-L1 signaling in the tumor microenvironment?","Question",{"text":112,"@type":113},"PD-1/PD-L1 signaling is described as a key factor in local immunosuppression and immune tolerance. It contributes to immune checkpoint regulation during chronic antigen encounter.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does interferon-gamma relate to exosomal PD-L1?",{"text":117,"@type":113},"IFN-g can stimulate cancer cells to release exosomal PD-L1 (exoPD-L1). Circulating exoPD-L1 levels correlate positively with IFN-g.",{"name":119,"@type":110,"acceptedAnswer":120},"Why might some patients be resistant to anti–PD-1/PD-L1 treatment?",{"text":121,"@type":113},"The review links resistance to exoPD-L1 lowering therapeutic response by mimicking or reinforcing PD-L1 effects on immune cells. 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Immunol. 15:1395332 .  \ndoi: 10.3389/fimmu.2024.1395332  \nCOPYRIGHT  \n© 2024 Lu and Yang. This is an open-access article distributed under the terms of the  \nCreative Commons Attribution License (CC BY) .  \nThe 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.  \nExosomal PD-L1 in cancer and other fields: recent advances and perspectives  \nMan-Man Lu 1 and Yu Yang 2*  \n1Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China, 2 Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China  \nPD-1/PD-L1 signaling is a key factor of local immunosuppression in the tumor microenvironment. Immune checkpoint inhibitors targeting PD-1/PD-L1 signaling have achieved tremendous success in clinic. However, several types of cancer are particularly refractory to the anti–PD-1/PD-L1 treatment. Recently, a series of studies reported that IFN-g can stimulate cancer cells to release exosomal PD-L1 (exoPD-L1), which possesses the ability to suppress anticancer immune responses and is associated with anti-PD-1 response. In this review, we introduce the PD-1/PD-L1 signaling, including the so-called ‘ reverse signaling ’. Furthermore, we summarize the immune treatments of cancers and pay more attention to immune checkpoint inhibitors targeting PD-1/PD-L1 signaling. Additionally, we review the action mechanisms and regulation of exoPD-L1 . We also introduce the function of exoPD-L1 as biomarkers. Finally, we review the methods for analyzing and quantifying exoPD-L1, the therapeutic strategies targeting exoPD-L1 to enhance immunotherapy and the roles of exoPD-L1 beyond cancer. This comprehensive review delves into recent advances of exoPD-L1 and all these findings suggest that exoPD-L1 plays an important role in both cancer and other fields.  \nKEYWORDS  \nexosome, PD-L1, immune checkpoint, exoso mal PD-L1, immunotherapy, resistance, biomarker  \n1 Introduction  \nProgrammed cell death protein 1 (PD-1) is one of the most famous co-inhibitory receptors on the surface of activated T cells (1) . Ligands of PD-1 include PD-L1 and PD-L2 . Both cancer cells and cancer stroma express PD-L1 and PD-L2 . However, antibodies against PD-1, which block both PD-L1 and PD-L2, show no obvious clinical advantage than antibodies against PD-L1, indicating PD-L1 is the dominant ligand of PD-1 in human tumor microenvironment (2) . Under physiological condition, the PD-1/PD-L1 signaling is involved in immune homeostasis and plays important role in immune tolerance. Upon recognition of antigens, T cells rapidly express PD-1 to modulate the strength of T cell  \nFrontiers in Immunology 01 [frontiersin.org](frontiersin.org)  \nactivation (TCA) . Cancer cells express tumor-related antigens continuously and, in such a setting of chronic antigen encounter, T cells express high level of PD-1 and become inept progressively. Accordingly, T cells lose effector functions and develop into an exhausted state (3) . A seminal study first reported cancer cells can release exosomes that carry PD-L1 on their surface (4) . This kind of exosomal PD-L1 (exoPD-L1) can be stimulated ","cbCaijCvI9TcHAv6","https://ap.wps.com/l/cbCaijCvI9TcHAv6","pdf",999986,13,"English","# Introduction\n## PD-1/PD-L1 signaling overview\n# ExoPD-L1: mechanisms, regulation, and clinical relevance\n## Action mechanisms and regulation of exoPD-L1\n## ExoPD-L1 as biomarkers\n## Analysis and quantification methods\n# Therapeutic strategies and broader roles\n## Targeting exoPD-L1 to enhance immunotherapy\n## Roles of exoPD-L1 beyond cancer","[{\"question\":\"What is the significance of PD-1/PD-L1 signaling in the tumor microenvironment?\",\"answer\":\"PD-1/PD-L1 signaling is described as a key factor in local immunosuppression and immune tolerance. It contributes to immune checkpoint regulation during chronic antigen encounter.\"},{\"question\":\"How does interferon-gamma relate to exosomal PD-L1?\",\"answer\":\"IFN-g can stimulate cancer cells to release exosomal PD-L1 (exoPD-L1). Circulating exoPD-L1 levels correlate positively with IFN-g.\"},{\"question\":\"Why might some patients be resistant to anti–PD-1/PD-L1 treatment?\",\"answer\":\"The review links resistance to exoPD-L1 lowering therapeutic response by mimicking or reinforcing PD-L1 effects on immune cells. Some cancers are particularly refractory to anti–PD-1/PD-L1 therapy.\"}]","Exosomal PD-L1 in cancer and other fields: recent advances and perspectives | PDF",1789996478,33]