Hepatoma cell-intrinsic TLR9 activation induces immune escape through PD-L1 upregulation in hepatocellular carcinoma
Binghai Zhou, Jiuliang Yan, Lei Guo, Bo Zhang, Shuang Liu, Mincheng Yu, Zheng Chen, Kewei Zhang, Wentao Zhang, Xiaoqiang Li, Yongfeng Xu, Yong‐Sheng Xiao, Jian Zhou, Jia Fan, Mien‐Chie Hung, Hui Li, Qing‐Hai Ye
Abstract
: We showed that hepatoma cell-intrinsic TLR9 activation regulated the crosstalk between PARP1 autoPARylation and ubiquitination and between STAT3 PARylation and phosphorylation, which together upregulated PD-L1 expression and finally induces immune escape. Therefore, combination therapy with a TLR9 agonist and an anti-PD-1 antibody or anti-PD-L1 had much better antitumor efficacy than either monotherapy in HCC.
Topics & Concepts
TLR9Cancer researchDownregulation and upregulationPhosphorylationSTAT3AgonistHepatocellular carcinomaBiologyChemistryReceptorCell biologyGene expressionBiochemistryDNA methylationGenePARP inhibition in cancer therapyCancer Immunotherapy and BiomarkersColorectal and Anal Carcinomas