| Title | Tobacco carcinogen induces tryptophan metabolism and immune suppression via induction of indoleamine 2,3-dioxygenase 1 |
| Authors | Liang, Fan Wang, Gui-Zhen Wang, Yan Yang, Ya-Ning Wen, Zhe-Sheng Chen, Dong-Ni Fang, Wen-Feng Zhang, Bin Yang, Lu Zhang, Chen Han, Si-Chong Yang, Fu-Ying Wang, Di Liang, Li-Jun Wang, Zheng Zhao, Yong Wang, Chang-Li Zhang, Li Zhou, Guang-Biao |
| Affiliation | Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, Natl Canc Ctr, Natl Clin Res Ctr Canc,State Key Lab Mol Oncol, Beijing, Peoples R China Chinese Acad Sci, Univ Chinese Acad Sci, Inst Zool, State Key Lab Membrane Biol, Beijing, Peoples R China Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Dept Med Oncol, Natl Clin Res Ctr Canc,Canc Hosp, Beijing, Peoples R China Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Med Oncol Dept, State Key Lab Oncol South China,Canc Ctr, Guangzhou, Peoples R China Tianjin Med Univ Canc Inst & Hosp, Tianjin Lung Canc Ctr, Natl Clin Res Ctr Canc, Tianjins Clin Res Ctr Canc,Dept Lung Canc,Key Lab, Tianjin, Peoples R China Peking Univ, Dept Med Oncol & Radiat Sickness, Hosp 3, Beijing, Peoples R China |
| Keywords | CIGARETTE-SMOKE T-CELLS NICOTINIC RECEPTOR LUNG EXPRESSION KYNURENINE HALLMARKS APOPTOSIS FEATURES CANCER |
| Issue Date | 7-Sep-2022 |
| Publisher | SIGNAL TRANSDUCTION AND TARGETED THERAPY |
| Abstract | Indoleamine 2,3-dioxygenase 1 (IDO1), the enzyme that catabolizes tryptophan (Trp) metabolism to promote regulatory T cells (Tregs) and suppress CD8(+) T cells, is regulated by several intrinsic signaling pathways. Here, we found that tobacco smoke, a major public health concern that kills 8 million people each year worldwide, induced IDO1 in normal and malignant lung epithelial cells in vitro and in vivo. The carcinogen nicotine-derived nitrosaminoketone (NNK) was the tobacco compound that upregulated IDO1 via activation of the transcription factor c-Jun, which has a binding site for the IDO1 promoter. The NNK receptor alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) was required for NNK-induced c-Jun activation and IDO1 upregulation. In A/J mice, NNK reduced CD8(+) T cells and increased Tregs. Clinically, smoker patients with non-small-cell lung cancer (NSCLC) exhibited high IDO1 levels and low Trp/kynurenine (Kyn) ratios. In NSCLC patients, smokers with lower IDO1 responded better to anti-PD1 antibody treatment than those with higher IDO1. These data indicate that tobacco smoke induces IDO1 to catabolize Trp metabolism and immune suppression to promote carcinogenesis, and lower IDO1 might be a potential biomarker for anti-PD1 antibodies in smoker patients, whereas IDO1-high smoker patients might benefit from IDO1 inhibitors in combination with anti-PD1 antibodies. |
| URI | http://hdl.handle.net/20.500.11897/654282 |
| ISSN | 2095-9907 |
| DOI | 10.1038/s41392-022-01127-3 |
| Indexed | SCI(E) |
| Appears in Collections: | 第三医院 |
