β-Catenin induces transcriptional expression of PD-L1 to promote glioblastoma immune evasion

• DOI: 10.1084/jem.20191115
• Publication Date: 2020-08-27T15:30:21Z
• Authors: Linyong Du; Jong-Ho Lee; Hongfei Jiang; Chengde Wang; Silu Wang; Zhihong Zheng; Fei Shao; Daqian Xu; Yan Xia; Jing Li; Yanhua Zheng; Xu Qian; Xinjian Li; Hyung-Ryong Kim; Dongming Xing; Pengyuan Liu; Zhimin Lu; Jianxin Lyu
• Keywords: Evasion (ethics); Beta-catenin

PD-L1 up-regulation in cancer contributes to immune evasion by tumor cells. Here, we show that Wnt ligand and activated EGFR induce the binding of β-catenin/TCF/LEF complex CD274 gene promoter region expression, which AKT activation plays an important role. β-Catenin depletion, inhibition, or PTEN expression reduces cells, enhances infiltration CD8+ T growth, accompanied prolonged mouse survival. Combined treatment with a clinically available inhibitor anti–PD-1 antibody overcomes greatly inhibits growth. In addition, AKT-mediated β-catenin S552 phosphorylation nuclear are positively correlated inversely cells human glioblastoma specimens, highlighting clinical significance evasion.