A selective HDAC8 inhibitor potentiates antitumor immunity and efficacy of immune checkpoint blockade in hepatocellular carcinoma
Weiqin Yang, Yu Feng, Jingying Zhou, Otto Ka-Wing Cheung, Jian Cao, Jing Wang, Wenshu Tang, Yalin Tu, Liangliang Xu, Feng Wu, Zhiwu Tan, Hanyong Sun, Yuan Tian, John Wong, Paul B.S. Lai, Stephen L. Chan, Anthony W.H. Chan, Patrick Tan, Zhiwei Chen, Joseph J.�Y. Sung, Kevin Y. Yip, Ka‐Fai To, Alfred S.L. Cheng
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.