Chidamide functions as a VISTA/PSGL-1 blocker for cancer immunotherapy.

IF 5.1 2区医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2025-02-11 DOI:10.1007/s00262-025-03955-y

Xiaoshuang Niu, Wenshan Zhao, Xiuman Zhou, Feiyu Luo, Youmei Xiao, Tao Luo, Xinghua Sui, Wanqiong Li, Qingyu Dong, Xin Yang, Zhuoying He, Wenzhi Shang, Yixuan Sun, Yanfeng Gao

{"title":"Chidamide functions as a VISTA/PSGL-1 blocker for cancer immunotherapy.","authors":"Xiaoshuang Niu, Wenshan Zhao, Xiuman Zhou, Feiyu Luo, Youmei Xiao, Tao Luo, Xinghua Sui, Wanqiong Li, Qingyu Dong, Xin Yang, Zhuoying He, Wenzhi Shang, Yixuan Sun, Yanfeng Gao","doi":"10.1007/s00262-025-03955-y","DOIUrl":null,"url":null,"abstract":"The response rates of PD-1/PD-L1 blockade in cancer immunotherapy are relatively low, necessitating the development of novel immune checkpoint inhibitors. Compared with other immune checkpoints, VISTA interacts with its ligand PSGL-1 only under acidic conditions in the tumor microenvironment to suppress the function of CD8+ T cells. On the other hand, drug repurposing offers advantages such as time efficiency and high safety. However, the development of VISTA/PSGL-1 inhibitor based on drug repurposing is still infancy. Here, by screening a library of marketed drugs, we identified Chidamide had a strong binding affinity toward VISTA (KD = 5 nM) and blocked VISTA/PSGL-1 under acidic conditions, thereby significantly enhancing the function of CD8+ T cells and inhibiting the tumor growth in immunocompetent murine CT26 tumor model. This study represents the first discovery of Chidamide as VISTA/PSGL-1 blocker for cancer immunotherapy.","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 3","pages":"104"},"PeriodicalIF":5.1000,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813839/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Immunology, Immunotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00262-025-03955-y","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The response rates of PD-1/PD-L1 blockade in cancer immunotherapy are relatively low, necessitating the development of novel immune checkpoint inhibitors. Compared with other immune checkpoints, VISTA interacts with its ligand PSGL-1 only under acidic conditions in the tumor microenvironment to suppress the function of CD8⁺ T cells. On the other hand, drug repurposing offers advantages such as time efficiency and high safety. However, the development of VISTA/PSGL-1 inhibitor based on drug repurposing is still infancy. Here, by screening a library of marketed drugs, we identified Chidamide had a strong binding affinity toward VISTA (K_D = 5 nM) and blocked VISTA/PSGL-1 under acidic conditions, thereby significantly enhancing the function of CD8⁺ T cells and inhibiting the tumor growth in immunocompetent murine CT26 tumor model. This study represents the first discovery of Chidamide as VISTA/PSGL-1 blocker for cancer immunotherapy.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

Chidamide 可作为 VISTA/PSGL-1 阻断剂用于癌症免疫疗法。

PD-1/PD-L1阻断在癌症免疫治疗中的应答率相对较低，需要开发新的免疫检查点抑制剂。与其他免疫检查点相比，VISTA仅在肿瘤微环境的酸性条件下与其配体PSGL-1相互作用，抑制CD8+ T细胞的功能。另一方面，药物再利用具有时间效率高、安全性高等优点。然而，基于药物再利用的VISTA/PSGL-1抑制剂的开发仍处于起步阶段。本研究通过筛选已上市药物文库，发现Chidamide对VISTA具有较强的结合亲和力（KD = 5 nM），在酸性条件下阻断VISTA/PSGL-1，从而显著增强CD8+ T细胞的功能，抑制免疫活性小鼠CT26肿瘤模型的肿瘤生长。这项研究首次发现了Chidamide作为癌症免疫治疗的VISTA/PSGL-1阻滞剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Cancer Immunology, Immunotherapy 医学-免疫学

CiteScore

10.50

自引率

1.70%

发文量

207

审稿时长

1 months

期刊介绍： Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.