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Within the liver’s inherently tolerogenic microenvironment, parenchymal, non-parenchymal and immune cell populations are engaged in a dynamic regulatory network mediated by PD-1/PD-L1, preserving immune homeostasis and balancing innate and adaptive immune responses. Aberrant PD-1/PD-L1 signaling is implicated across chronic liver disorders, and a systematic synthesis reviews regulatory roles and recent advances in multiple disease settings.",{"@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/the-role-of-pd-1pd-l1-axis-in-liver-diseases/450235/",{"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-role-of-pd-1pd-l1-axis-in-liver-diseases/450235.png","ImageObject",300,407,{"name":92,"@type":93},"Levi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-03","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the role of the PD-1/PD-L1 axis in the liver microenvironment?","Question",{"text":112,"@type":113},"The PD-1/PD-L1 signaling axis helps maintain immune suppression within the liver’s tolerogenic microenvironment, supporting immune homeostasis and coordinated innate–adaptive responses.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which chronic liver diseases are associated with aberrant PD-1/PD-L1 signaling?",{"text":117,"@type":113},"Aberrant signaling is implicated across a disease continuum including viral hepatitis, fibrosis, and hepatic malignancy.",{"name":119,"@type":110,"acceptedAnswer":120},"What topics does the review cover regarding PD-1/PD-L1 in liver cancer?",{"text":121,"@type":113},"It summarizes mechanisms regulating PD-1/PD-L1 expression and function in hepatocellular carcinoma, including tumor microenvironment determinants, intracellular signaling cascades, post-translational modifications, and epigenetic control.","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},450235,1791034612,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"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},7971461740909,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Clinical and Experimental Medicine (2026) 26:87  \n[https://doi.org/10.1007/s10238-025-01982-8](https://doi.org/10.1007/s10238-025-01982-8)  \nREVIEW  \nThe role of PD‑1/PD‑L1 axis in liver diseases  \nZijian Zeng1,2 · Shuanglan Chen1,2 · Qun Niu1,2 · Haijian Dong1,2 · Yuanqian Yao1,2 · Kaixin Wang1,2 · Xueqing Gong1,2 · Hui Li1  \nReceived: 7 October 2025 / Accepted: 21 November 2025 © The Author(s) 2025  \nAbstract  \nThe programmed cell death protein 1 (PD‑1)/programmed death‑ligand 1 (PD‑L1) signaling axis is recognized as a cen‑ tral pathway maintaining immune suppression. Within the liver’s inherently tolerogenic microenvironment, parenchymal, non‑parenchymal and immune cell populations are engaged in a dynamic regulatory network mediated by PD‑1/PD‑L1, which serves to preserve immune homeostasis and to balance innate and adaptive immune responses. Aberrant PD‑1/ PD‑L1 signaling has been implicated across the disease continuum of many chronic liver disorders, spanning viral hepa‑ titis, fibrosis, and hepatic malignancy. A systematic synthesis is presented of the regulatory roles and recent advances concerning the PD‑1/PD‑L1 axis in viral hepatitis, metabolic dysfunction‑associated fatty liver disease (MAFLD), auto‑ immune liver diseases and related conditions. Mechanisms regulating PD‑1/PD‑L1 expression and function in hepatocel‑ lular carcinoma (HCC) are comprehensively summarized, including tumor microenvironmental determinants, intracellular signaling cascades, post‑translational modifications and epigenetic control. A theoretical framework and novel perspectives are thereby provided for elucidating PD‑1/PD‑L1 dysregulation in chronic liver disease, for identifying candidate biomark‑ ers, and for informing the development of precision immunotherapeutic strategies.  \nKeywords PD‑ 1 · PD‑L1 · Chronic liver diseases · HCC · Regulatory mechanism  \nAbbreviations  \n3’‑UTRAPCcircRNACTL  \nDC HBV‑HCCHCCHIF‑α HSC  \nICI IFN‑γ KCs  \n3’‑untranslated region antigen‑presenting cell  \ncircular RNAs  \ncytotoxic T lymphocyte  \ndendritic cell  \nHBV‑related hepatocellular carcinoma hepatocellular carcinoma hypoxia‑inducible factor alpha hepatic stellate cell  \nimmune checkpoint inhibitor interferon‑gamma  \nKupffer cells  \n􀀍 Hui Li [1400124746@qq.com](1400124746@qq.com)  \n1 Hospital of Chengdu University of Traditional Chinese Medicine, TCM Hospital of Sichuan Province, Chengdu, Sichuan, China  \n2 School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China  \nlncRNA LSEC  \nm6AMAFLD‑HCC  \nMAIT miRNA mRNA NKPD‑ 1  \nPD‑L1  \nPD‑L2 sPD‑L1 TAM Tem Temra  \nTfh  \nTIL  \nTMETreg  \nTrm  \nlong non‑coding RNA  \nliver sinusoidal endothelial cell N6‑methyladenosine MAFLD‑associated hepatocellular carcinoma  \nmucosal‑associated invariant T cells microRNA  \nmessenger RNA natural killer cells  \nprogrammed cell death protein 1  \nprogrammed death‑ligand 1  \nProgrammed death‑ligand 2  \nsoluble programmed death‑ligand 1 tumor‑associated macrophage effector memory T cells  \nterminally differentiated effector memory  \nT cells re‑expressing CD45RA follicular helper T cell tumor‑infiltrating lymphocyte tumor immune microenvironment regulatory T cells tissue‑resident memory T cells  \n1 3  \nIntroduction  \nThe liver is characterized by a unique immune‑tolerant microenvironment, a feature that is determined by its core physiological functions, including receipt of portal venous blood enriched in dietary antigens and microbial products and participation in systemic metabolism and detoxifica‑ tion. This immune‑tolerant milieu is formed by the spe‑ cialized architecture of hepatic sinusoids and by distinct resident cell populations, notably liver sinusoidal endo‑ thelial cells (LSECs), Kupffer cells (KCs) and tolerogenic dendritic cells (tolDCs) . Immune‑checkpoint molecules, exemplified by programmed cell death protein 1 (PD‑1) and its ligand programmed death‑ligand 1 (PD‑L1), together with immunosuppressive cytokines such as interle","cbCaig1Aw1IhNO4t","https://ap.wps.com/l/cbCaig1Aw1IhNO4t","pdf",2317514,28,"English","# Introduction\n## PD-1/PD-L1 in hepatic immune tolerance\n# Abstract\n## Regulatory roles and recent advances in chronic liver diseases\n# Keywords\n## PD-1/PD-L1 and major disease associations","[{\"question\":\"What is the role of the PD-1/PD-L1 axis in the liver microenvironment?\",\"answer\":\"The PD-1/PD-L1 signaling axis helps maintain immune suppression within the liver’s tolerogenic microenvironment, supporting immune homeostasis and coordinated innate–adaptive responses.\"},{\"question\":\"Which chronic liver diseases are associated with aberrant PD-1/PD-L1 signaling?\",\"answer\":\"Aberrant signaling is implicated across a disease continuum including viral hepatitis, fibrosis, and hepatic malignancy.\"},{\"question\":\"What topics does the review cover regarding PD-1/PD-L1 in liver cancer?\",\"answer\":\"It summarizes mechanisms regulating PD-1/PD-L1 expression and function in hepatocellular carcinoma, including tumor microenvironment determinants, intracellular signaling cascades, post-translational modifications, and epigenetic control.\"}]","The role of PD-1/PD-L1 axis in liver diseases | PDF",1790732594,71]