[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-373217-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-373217-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","utilization-of-exosome-based-therapies-to-augment-anti-pd-1pd-l1-therapies","Utilization of exosome-based therapies to augment anti-PD-1/PD-L1 therapies","","Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have reshaped cancer care, yet therapeutic resistance remains common. Resistance can arise through alternative immune checkpoints, T-cell exhaustion, low tumor burden, and immunosuppressive tumor microenvironment cells. Tumor-derived exosomes carrying PD-L1 may contribute by locally and systemically dampening immune function. Blocking exosome secretion has shown preclinical promise, supporting combined strategies with current anti-PD-1/PD-L1 therapies.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/utilization-of-exosome-based-therapies-to-augment-anti-pd-1pd-l1-therapies/373217/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/utilization-of-exosome-based-therapies-to-augment-anti-pd-1pd-l1-therapies/373217.png","ImageObject",300,407,{"name":42,"@type":43},"Jake","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",16,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why do anti-PD-1/PD-L1 therapies fail in some patients?","Question",{"text":63,"@type":64},"Resistance can involve alternative immune checkpoints, T-cell exhaustion, low tumor mutational burden, and immunosuppressive cells within the tumor microenvironment that blunt PD-1/PD-L1 signaling.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do tumor-derived exosomes contribute to resistance?",{"text":68,"@type":64},"Tumor-derived exosomes expressing PD-L1 can suppress immune responses both locally and systemically, supporting immune evasion and limiting the effectiveness of anti-PD-1/PD-L1 treatment.",{"name":70,"@type":61,"acceptedAnswer":71},"What evidence supports inhibiting exosome secretion to enhance PD-1/PD-L1 blockade?",{"text":72,"@type":64},"Preclinical studies indicate that inhibiting exosome secretion can improve responses to anti-PD-L1 therapy, and multiple tumor models show exosome-driven immunosuppression consistent with a druggable mechanism.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},373217,1790639381,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":30,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":111},962084928904,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Open access Commentary  \n Utilization of exosome-based therapies to augment anti-PD-1/PD-L1 therapies  \nJohn S. Wang,1 Samer Yassin,1 Adam Y. Lin  2,3  \nTo cite: Wang JS, Yassin S, Lin AY. Utilization of exosomebased therapies to augment anti-PD-1/PD-L1 therapies. Journal for ImmunoTherapy of Cancer 2025;13:e010603 . doi:10.1136/jitc-2024-010603  \nAccepted 10 April 2025  \n© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.  \n1McGaw Medicine CenterInternal Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA 2Division of Hematology Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA 3Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA  \nCorrespondence to  \nDr Adam Y. Lin;  \n[adam.lin@northwestern.edu](adam.lin@northwestern.edu)  \nAbstract The development of immune checkpoint inhibitors targeting the programmed cell death 1 (PD- 1)/programmed cell death ligand 1 (PD-L1) pathway has significantly transformed the landscape of cancer treatment. However, resistance mechanisms such as alternative immune checkpoints, T-cell exhaustion, low tumor burden, and immunosuppressive cells in the tumor microenvironment can limit therapeutic efficacy. Recent research has highlighted the role of tumor-derived exosomes expressing PD-L1, which may contribute to resistance by locally and systemically suppressing immune responses. Inhibiting exosome secretion has shown promise in enhancing the effectiveness of anti-PD-1/PD-L1 therapies. The therapeutic potential of targeting exosomesto improve PD-1/PD-L1 inhibition is gaining attention, with preclinical studies showing encouraging results. Clinical trials are needed to evaluate the combination of exosome secretion inhibitors with existing checkpoint therapies and provide hope for patients with resistant cancers.  \nCOMMENTARY  \nThe introduction of immune checkpoint inhibitors that target the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway has significantly transformed the landscape of cancer therapy since the approval of the first drug in its class, pembrolizumab, in 2014. PD-1 and PD-L1 form an immune checkpoint that is known to suppress the T-cell immune response. In the realm of T-cell biology, it has received particular attention for its role in modulating tumor cell immune tolerance. Tumor cells express PD-L1, which interacts with PD-1 on T cells, inducing apoptotic pathways and downregulating the immune response within the tumor microenvironment.1 Therefore, pharmacologic inhibition of the PD-1/PD-L1 interaction prevents tumor cells from evading the immune system and has demonstrated efficacy in a variety of solid tumors, including but not limited to melanoma, non-small cell lung cancer, urothelial carcinoma, and hepatocellular carcinoma.1  \nAs we eclipse more than a decade since the approval of the first checkpoint inhibitor, weare observing an increasing number of patients who have enjoyed durable responses for tumor types that previously had devastatingly  \npoor outcomes. Over the last decade, longterm survival curves for patients with unresectable advanced melanoma receiving pembrolizumab or ipilimumab from the KEYNOTE-006 trial have been closely monitored. Pembrolizumab’s efficacy in advanced melanoma was confirmed with the following results: (1) the pembrolizumab group hada median melanoma-specific survival of 51.8 months compared with (2) the ipilimumab group’s median melanoma-specific survival of 17.2 months.2 After 10 years, both survival curves exhibited a stable tail end, supporting the idea that these patients may even be cured of their metastatic disease. However, there are subsets of patients whose tumors show resistance patterns and have no clinical response to therapy. Possible mechanisms of resistance include: (1) alternati","cbCaiuloJkLlJSDG","https://ap.wps.com/l/cbCaiuloJkLlJSDG","pdf",183786,"English","# Abstract\n# PD-1/PD-L1 checkpoint biology and therapeutic impact\n## Mechanisms of resistance\n# Role of tumor-derived exosomes expressing PD-L1\n## Preclinical evidence and examples\n# Therapeutic strategies targeting exosomal PD-L1","[{\"question\":\"Why do anti-PD-1/PD-L1 therapies fail in some patients?\",\"answer\":\"Resistance can involve alternative immune checkpoints, T-cell exhaustion, low tumor mutational burden, and immunosuppressive cells within the tumor microenvironment that blunt PD-1/PD-L1 signaling.\"},{\"question\":\"How do tumor-derived exosomes contribute to resistance?\",\"answer\":\"Tumor-derived exosomes expressing PD-L1 can suppress immune responses both locally and systemically, supporting immune evasion and limiting the effectiveness of anti-PD-1/PD-L1 treatment.\"},{\"question\":\"What evidence supports inhibiting exosome secretion to enhance PD-1/PD-L1 blockade?\",\"answer\":\"Preclinical studies indicate that inhibiting exosome secretion can improve responses to anti-PD-L1 therapy, and multiple tumor models show exosome-driven immunosuppression consistent with a druggable mechanism.\"}]","Utilization of exosome-based therapies to augment anti-PD-1/PD-L1 therapies | PDF",1790197994]