{"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":"<p><p>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<sup>+</sup> 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<sub>D</sub> = 5 nM) and blocked VISTA/PSGL-1 under acidic conditions, thereby significantly enhancing the function of CD8<sup>+</sup> 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.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 3","pages":"104"},"PeriodicalIF":4.6000,"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 (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.
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.
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