The Aryl hydrocarbon receptor mediates tobacco-induced PD-L1 expression and is associated with response to immunotherapy

• Published in: Nature communications Vol. 10; no. 1; pp. 1125 - 13
• Main Authors: Wang, Gui-Zhen, Zhang, Li, Zhao, Xin-Chun, Gao, San-Hui, Qu, Li-Wei, Yu, Hong, Fang, Wen-Feng, Zhou, Yong-Chun, Liang, Fan, Zhang, Chen, Huang, Yun-Chao, Liu, Zhihua, Fu, Yang-Xin, Zhou, Guang-Biao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.03.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 13/51; 13/89; 13/95; 38/88; 42/89; 631/67/1612/1350; 692/4028/67/1612/1350; 82/1; 96/44; Adaptive immunity; Animal models; Animals; Antibodies; Antibodies, Monoclonal - pharmacology; Anticancer properties; Antitumor activity; Aromatic compounds; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - genetics; B7-H1 Antigen - immunology; Benzo(a)pyrene; Benzo(a)pyrene - toxicity; Benzoflavones - pharmacology; Cancer; Carcinogenesis; Carcinogens; Carcinogens - toxicity; Cell Line, Tumor; Cigarette smoke; Disease Models, Animal; Epithelial cells; Epithelium; Female; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Hydrocarbons; Immunity; Immunotherapy; Immunotherapy - methods; Lung - drug effects; Lung - immunology; Lung - pathology; Lung cancer; Lung Neoplasms - etiology; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Lung Neoplasms - therapy; Mice; Mice, Inbred C57BL; Monoclonal antibodies; multidisciplinary; Patients; PD-1 protein; PD-L1 protein; Pembrolizumab; Pyrene; Receptors; Receptors, Aryl Hydrocarbon - antagonists & inhibitors; Receptors, Aryl Hydrocarbon - genetics; Receptors, Aryl Hydrocarbon - immunology; Science; Signal Transduction; Small Cell Lung Carcinoma - etiology; Small Cell Lung Carcinoma - genetics; Small Cell Lung Carcinoma - mortality; Small Cell Lung Carcinoma - therapy; Smoke; Smoking; Smoking - adverse effects; Survival Analysis; Synergism; Targeted cancer therapy; Therapeutic applications; Therapeutic targets; Tobacco; Tobacco smoke; Tumorigenesis; Xenograft Model Antitumor Assays

Whether tobacco carcinogens enable exposed cells immune escape resulting in carcinogenesis, and why patients who smoke respond better to immunotherapies than non-smokers, remains poorly understood. Here we report that cigarette smoke and the carcinogen benzo(a)pyrene (BaP) induce PD-L1 expression on...