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Chidamide functions as a VISTA/PSGL-1 blocker for cancer immunotherapy
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Chidamide functions as a VISTA/PSGL-1 blocker for cancer immunotherapy
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Journal Article
Chidamide functions as a VISTA/PSGL-1 blocker for cancer immunotherapy
2025
Overview
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.
Publisher
Springer Berlin Heidelberg,Springer Nature B.V,Springer
Subject
/ Aminopyridines - therapeutic use
/ Animals
/ Benzamides - therapeutic use
/ Cancer
/ CD8-Positive T-Lymphocytes - drug effects
/ CD8-Positive T-Lymphocytes - immunology
/ Female
/ Humans
/ Immune checkpoint inhibitors
/ Ligands
/ Medicine
/ Membrane Glycoproteins - antagonists & inhibitors
/ Membrane Glycoproteins - metabolism
/ Mice
/ Oncology
/ P-selectin glycoprotein ligand 1
/ Proteins
/ Software
/ Tumor Microenvironment - drug effects
/ Tumor Microenvironment - immunology
/ Tumors
/ VISTA
