Class I HDAC inhibitors enhance antitumor efficacy and persistence of CAR-T cells by activation of the Wnt pathway

• Published in: Cell reports (Cambridge) Vol. 43; no. 4; p. 114065
• Main Authors: Zhu, Meng, Han, Yingli, Gu, Tianning, Wang, Rui, Si, Xiaohui, Kong, Delin, Zhao, Peng, Wang, Xiujian, Li, Jinxin, Zhai, Xingyuan, Yu, Zebin, Lu, Huan, Li, Jingyi, Huang, He, Qian, Pengxu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.04.2024; Elsevier
• Subjects: Aminopyridines; Animals; Benzamides - pharmacology; CAR-T; Cell Line, Tumor; CP: Cancer; exhaustion; HDAC inhibitors; Histone Deacetylase 1 - metabolism; Histone Deacetylase Inhibitors - pharmacology; Humans; Immunotherapy, Adoptive - methods; memory T cell subsets; Mice; Receptors, Chimeric Antigen - metabolism; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Wnt signaling pathway; Wnt Signaling Pathway - drug effects; exhaustion; HDAC inhibitors; Wnt signaling pathway; CAR-T; CP: Cancer; memory T cell subsets

Epigenetic modification shapes differentiation trajectory and regulates the exhaustion state of chimeric antigen receptor T (CAR-T) cells. Limited efficacy induced by terminal exhaustion closely ties with intrinsic transcriptional regulation. However, the comprehensive regulatory mechanisms remain l...