文献类型：期刊文献

英文题名：Bromo- and extraterminal domain protein inhibition improves immunotherapy efficacy in hepatocellular carcinoma

作者：Liu, Chen[1,2];Miao, Xiaolong[1,2];Wang, Yao[3];Wen, Liang[4];Cheng, Xiawei[5];Kong, Deqiang[1,2];Zhao, Pengwei[6,7];Song, Dandan[6,7];Wang, Xinyi[6,7];Ding, Xianfeng[3];Xia, Hongguang[8];Wang, Weilin[1,2];Sun, Qiming[6,7];Gong, Weihua[1,2]

机构：[1]Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Surg, Hangzhou, Peoples R China;[2]Zhejiang Univ, Canc Ctr, Hangzhou, Peoples R China;[3]Zhejiang Sci Tech Univ, Coll Life Sci & Med, Hangzhou, Peoples R China;[4]Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Hepatobiliary Surg, Hangzhou, Peoples R China;[5]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Synthet Biol & Biotechnol Lab, Shanghai, Peoples R China;[6]Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Biochem, Hangzhou, Peoples R China;[7]Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Cardiol, Hangzhou, Peoples R China;[8]Zhejiang Univ, Sch Med, Dept Biochem & Mol Biol, Hangzhou, Peoples R China

年份：2020

卷号：111

期号：10

起止页码：3503

外文期刊名：CANCER SCIENCE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000560555800001)】；

基金：National Natural Science Foundation of China, Grant/Award Number: 81470527 and 81870306; Fundamental Research Funds for the Central Universities, Grant/Award Number: 2015XZZX004-21; Zhejiang Provincial 151 Talent Project, and Zhejiang Provincial Outstanding Youth Foundation, Grant/Award Number: LR13H020001; National Science Foundation for Outstanding Young Scholars of China, Grant/Award Number: 81522006

语种：英文

外文关键词：BET protein; hepatocellular carcinoma; immunotherapy; JQ1; PD-L1

摘要：Hepatocellular carcinoma (HCC) represents the majority of liver cancer and is the fourth most common cause of cancer-related death. Although advances in molecular targeted therapy have shown promise, none of these agents has yet demonstrated significant clinical benefit. Bromo- and extraterminal domain (BET) protein inhibitors have been considered potential therapeutic drugs for HCC but the biological activity remains unclear. This study found that BET protein inhibition did not effectively suppress the progression of HCC, using a transgenic HCC mouse model. Mechanistically, the BET protein inhibitor JQ1 upregulated the expression of programmed cell death-ligand 1 (PD-L1) on the plasma membrane in vivo and in vitro. Moreover, JQ1 enhanced the expression of Rab8A, which upregulated the expression of PD-L1 on the plasma membrane. This study also showed that JQ1 combined with anti-PD-L1 Ab effectively suppressed HCC progression, and this benefit was obtained by enhancing the activation and cytotoxic capabilities of CD8 T cells. These results revealed the crucial role and regulation of BET protein inhibition on the expression of PD-L1 in HCC. Thus, combining BET protein inhibition with immune checkpoint blockade offers an efficient therapeutic approach for HCC.