A selective HDAC8 inhibitor potentiates antitumor immunity and efficacy of immune checkpoint blockade in hepatocellular carcinoma
Weiqin Yang(Chinese University of Hong Kong), Yu Feng(Chinese University of Hong Kong), Jingying Zhou(Chinese University of Hong Kong), Otto Ka-Wing Cheung(Chinese University of Hong Kong), Jian Cao(Chinese University of Hong Kong), Jing Wang(Chinese University of Hong Kong), Wenshu Tang(Chinese University of Hong Kong), Yalin Tu(Chinese University of Hong Kong), Liangliang Xu(Chinese University of Hong Kong), Feng Wu(Chinese University of Hong Kong), Zhiwu Tan(Institute of Infection and Immunity), Hanyong Sun(Shanghai Jiao Tong University), Yuan Tian(Shenzhen University Health Science Center), John Wong(Chinese University of Hong Kong), Paul B.S. Lai(Chinese University of Hong Kong), Stephen L. Chan(Chinese University of Hong Kong), Anthony W.H. Chan(Chinese University of Hong Kong), Patrick Tan(SingHealth), Zhiwei Chen(Institute of Infection and Immunity), Joseph J.�Y. Sung(Sun Yat-sen University), Kevin Y. Yip(Chinese University of Hong Kong), Ka‐Fai To(Chinese University of Hong Kong), Alfred S.L. Cheng(Chinese University of Hong Kong)
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Abstract
T cells and potentiated eradication of established hepatomas by anti-PD-L1 therapy without evidence of toxicity. Mice treated with HDAC8 and PD-L1 coblockade were protected against subsequent tumor rechallenge as a result of the induction of memory T cells and remained tumor-free for greater than 15 months. Collectively, our study demonstrates that selective HDAC8 inhibition elicits effective and durable responses to ICB by co-opting adaptive immunity through enhancer reprogramming.
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