首页 / 院系成果 / 成果详情页

Genomic ERBB2/ERBB3 mutations promote PD-L1-mediated immune escape in gallbladder cancer: a whole-exome sequencing analysis 期刊论文

编号：

d199d848-45ff-4880-84b3-eb192703ec87
作者：

Li, Maolan#^[1,2]Liu, Fatao#^[2]Zhang, Fei#^[1,2]Zhou, Weiping#^[3]Jiang, Xiaoqing#^[4]Yang, Yuan^[3];Qu, Kai^[5];Wang, Yueqi(王越琦)^[6]Ma, Qiang^[1,2];Wang, Ting^[2];Bai, Lu^[2];Wang, Zheng^[1,2];Song, Xiaoling^[1,2];Zhu, Yidi^[1,2];Yuan, Ruiyan^[1,2];Gao, Yuan^[1,2];Liu, Yongchen^[1,2];Jin, Yunpeng^[1,2];Li, Huaifeng^[1,2];Xiang, Shanshan^[1,2];Ye, Yuanyuan^[1,2];Zhang, Yijian^[2];Jiang, Lin^[2];Hu, Yunping^[2];Hao, Yajuan^[2];Lu, Wei^[1,2];Chen, Shili^[2];Gu, Jun^[1,2];Zhou, Jian^[2];Gong, Wei^[1,2];Zhang, Yong^[1];Wang, Xuefeng^[1,2];Liu, Xiyong^[7];Liu, Chang^[5];Liu, Houbao(刘厚宝)*^[6]Liu, Yun*^[8]Liu, Yingbin*^[1,2]
语种：

英文
期刊：

GUT ISSN：0017-5749 2019 年 68 卷 6 期 (1024 - 1033) ; JUN
收录：
摘要：

Objectives Patients with gallbladder carcinoma (GBC) lack effective treatment methods largely due to the inadequacy of both molecular characterisation and potential therapeutic targets. We previously uncovered a spectrum of genomic alterations and identified recurrent mutations in the ErbB pathway in GBC. Here, we aimed to study recurrent mutations of genes and pathways in a larger cohort of patients with GBC and investigate the potential mechanisms and clinical significance of these mutations. Design We performed whole-exome sequencing (WES) in 157 patients with GBC. Functional experiments were applied in GBC cell lines to explore the oncogenic roles of ERBB2/ ERBB3 hotspot mutations, their correlation with PD-L1 expression and the underlying mechanisms. ERBB inhibitors and a PD-L1 blocker were used to evaluate the anticancer activities in co-culture systems in vitro and in vivo. Results WES identified ERBB2 and ERBB3 mutations at a frequency of 7%-8% in the expanded cohort, and patients with ERBB2/ ERBB3 mutations exhibited poorer prognoses. A set of in vitro and in vivo experiments revealed increased proliferation/ migration on ERBB2/ ERBB3 mutation. Ectopic expression of ERBB2/ ERBB3 mutants upregulated PD-L1 expression in GBC cells, effectively suppressed normal T-cellmediated cytotoxicity in vitro through activation of the PI3K/ Akt signalling pathway and contributed to the growth and progression of GBC in vivo. Treatment with an ERBB2/ ERBB3 inhibitor or a PD-L1 monoclonal antibody reversed these immunosuppressive effects, and combined therapy revealed promising therapeutic activities. Conclusions ERBB2/ ERBB3 mutations may serve as useful biomarkers in identifying patients who are sensitive to ERBB2/ ERBB3 inhibitors and PD-L1 monoclonal antibody treatment.
推荐引用方式
GB/T 7714：

Li Maolan,Liu Fatao,Zhang Fei, et al. Genomic ERBB2/ERBB3 mutations promote PD-L1-mediated immune escape in gallbladder cancer: a whole-exome sequencing analysis [J].GUT,2019,68(6):1024-1033.
APA：

Li Maolan,Liu Fatao,Zhang Fei,Zhou Weiping,&Liu Yingbin.(2019).Genomic ERBB2/ERBB3 mutations promote PD-L1-mediated immune escape in gallbladder cancer: a whole-exome sequencing analysis .GUT,68(6):1024-1033.
MLA：

Li Maolan, et al. "Genomic ERBB2/ERBB3 mutations promote PD-L1-mediated immune escape in gallbladder cancer: a whole-exome sequencing analysis" .GUT 68,6(2019):1024-1033.
条目包含文件：

文件类型：PDF,文件大小：

正在加载全文

未找到全文

浏览次数：35  下载次数：0

分享到：

浏览次数：35

下载次数：0

打印次数：0