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VISTA, an inhibitory V-domain Ig suppressor of T-cell activation and B7-family member, is expressed on hematopoietic cells and can strongly suppress T-cell function and anti-tumor immunity. This review explains VISTA’s expression and functional roles across cancers, summarizes candidate ligands and tumor microenvironment pathways, and closes with an overview of current clinical trials.",{"@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/vista-an-emerging-immune-checkpoint-with-clinical-relevance-across-diverse-malignancies/456284/",{"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/vista-an-emerging-immune-checkpoint-with-clinical-relevance-across-diverse-malignancies/456284.png","ImageObject",300,407,{"name":92,"@type":93},"Mary Man","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-30",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 is VISTA being considered as a therapeutic target instead of only targeting PD-1/PD-L1?","Question",{"text":112,"@type":113},"Anti-PD-1/PD-L1 therapy shows limited efficacy in several cancers, prompting exploration of other immune checkpoints. VISTA is presented as a promising alternative inhibitory checkpoint.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What role does VISTA play in anti-tumor immunity?",{"text":117,"@type":113},"VISTA is expressed on hematopoietic cells and inhibits T-cell function, suppressing anti-tumor immune responses in the tumor microenvironment.",{"name":119,"@type":110,"acceptedAnswer":120},"What does the review cover regarding VISTA’s clinical development?",{"text":121,"@type":113},"It highlights VISTA expression and roles across cancer types, discusses potential VISTA ligands and relevant pathways in the tumor microenvironment, and concludes with an overview of the latest clinical trials.","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},456284,1791310181,{"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":56,"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,"preview_page_count":4},7421720224475,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Immune Netw. 2025 Dec;25(6):e44 [https://doi.org/10.4110/in.2025.25.e44](https://doi.org/10.4110/in.2025.25.e44)[ ](https://doi.org/10.4110/in.2025.25.e44)pISSN 1598-2629·eISSN 2092-6685  \nReview Article  \nReceived: Nov 26, 2025  \nRevised: Dec 5, 2025  \nAccepted: Dec 5, 2025  \nPublished online: Dec 24, 2025  \n*Correspondence to  \nAbdallah Badou  \nImmunogenetics and Human Pathology Laboratory, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University, Rue Tarik Ibnou Ziad, Casablanca 20250, Morocco. Email: [abdallah.badou@univh2c.ma](abdallah.badou@univh2c.ma)  \n†Hiba Laraki and Ibtissam Rezouki contributed equally to this work.  \nCopyright © 2025. The Korean Association of Immunologists  \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ([https://](https://)[ ](https://)[creativecommons.org/licenses/by-nc/4.0/](creativecommons.org/licenses/by-nc/4.0/)) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.  \nORCID iDs  \nHiba Laraki  [https://orcid.org/0009-0009-5639-3302](https://orcid.org/0009-0009-5639-3302)[ ](https://orcid.org/0009-0009-5639-3302)Ibtissam Rezouki  [https://orcid.org/0009-0008-1669-6993](https://orcid.org/0009-0008-1669-6993)[ ](https://orcid.org/0009-0008-1669-6993)Khalil Choukri  [https://orcid.org/0000-0003-3534-8237](https://orcid.org/0000-0003-3534-8237)[ ](https://orcid.org/0000-0003-3534-8237)Abdallah Badou  [https://orcid.org/0000-0003-4849-9085](https://orcid.org/0000-0003-4849-9085)  \nAbbreviations  \naa, amino acid; AML, acute myeloid leukemia; APC, Ag-presenting cells; ccRCC, clear cell renal cell carcinoma; CRC, colorectal cancer;  \nVISTA: An Emerging Immune Checkpoint With Clinical Relevance Across Diverse Malignancies  \nHiba Laraki  †, Ibtissam Rezouki  †, Khalil Choukri , Abdallah Badou  *  \nImmunogenetics and Human Pathology Laboratory, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University, Casablanca 20250, Morocco  \nABSTRACT  \nImmune checkpoint inhibitors (ICIs) offer tremendous promise as therapeutic targets fora range of tumor types, and their development is advancing rapidly in cancer treatment. Nevertheless, the limited efficacy of anti-PD-1/PD-L1 immunotherapy in several cancers has driven researchers to explore other immune checkpoints as potential therapeutic targets. The inhibitory V-domain Ig suppressor of T-cell activation (VISTA) appears to be a captivating candidate. As a member of the B7 family, VISTA is expressed on hematopoietic cells and has the ability to significantly suppress T cell function and the anti-tumor immune response. In this review, our objective is to shed light on the multifaceted potential of VISTA as a therapeutic target. We will highlight the expressions and role of VISTA in various cancer types. Subsequently, we will go through distinct potential VISTA ligands, while underscoring the role of the pathway within the tumor microenvironments (TME). Finally, we will conclude with a comprehensive overview of the latest clinical trials, highlighting VISTA's emerging potential in cancer treatment.  \nKeywords: Immune checkpoint inhibitors; VSIR protein, human; Tumor microenvironment; Clinical trial  \nINTRODUCTION  \nCancer remains one of the leading causes of death worldwide, with an estimated  \n10 million deaths in 2020 (1) . While conventional treatments such as surgery, radiotherapy, chemotherapy, and hormone therapy have improved patients’ outcomes, their associated toxicities and limited efficacy in certain malignancies have underscored the need for more targeted and effective strategies. In this context, cancer immunotherapy has emerged as a transformative approach aimed at harnessing the immune system to recognize and eliminate tumors cells. Immunotherapy encompasses various approaches, including vaccines, adoptive T cell transfer, cytokine therapy, and monoclonal Abs (2-5) .  \nAmon","cbCaivJDimT57QKQ","https://ap.wps.com/l/cbCaivJDimT57QKQ","pdf",1497691,"English","# Abstract\n# Introduction\n## Cancer immunotherapy and immune checkpoints\n# VISTA as an inhibitory immune checkpoint\n## Expression, roles, and mechanisms in tumors\n# VISTA ligands and tumor microenvironment pathways\n# Clinical trials overview\n# Conflict of Interest\n# Author Contributions","[{\"question\":\"Why is VISTA being considered as a therapeutic target instead of only targeting PD-1/PD-L1?\",\"answer\":\"Anti-PD-1/PD-L1 therapy shows limited efficacy in several cancers, prompting exploration of other immune checkpoints. VISTA is presented as a promising alternative inhibitory checkpoint.\"},{\"question\":\"What role does VISTA play in anti-tumor immunity?\",\"answer\":\"VISTA is expressed on hematopoietic cells and inhibits T-cell function, suppressing anti-tumor immune responses in the tumor microenvironment.\"},{\"question\":\"What does the review cover regarding VISTA’s clinical development?\",\"answer\":\"It highlights VISTA expression and roles across cancer types, discusses potential VISTA ligands and relevant pathways in the tumor microenvironment, and concludes with an overview of the latest clinical trials.\"}]","VISTA: An Emerging Immune Checkpoint With Clinical Relevance Across Diverse Malignancies | PDF",1790745470,48]