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Tobacco carcinogen induces tryptophan metabolism and immune suppression via induction of indoleamine 2,3-dioxygenase 1

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9448807/
https://www.ncbi.nlm.nih.gov/pubmed/36068203
http://dx.doi.org/10.1038/s41392-022-01127-3
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author 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
author_facet 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
author_sort Liang, Fan
collection PubMed
description 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 α7 nicotinic acetylcholine receptor (α7nAChR) 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.
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spelling pubmed-94488072022-09-08 Tobacco carcinogen induces tryptophan metabolism and immune suppression via induction of indoleamine 2,3-dioxygenase 1 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 Signal Transduct Target Ther Article 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 α7 nicotinic acetylcholine receptor (α7nAChR) 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. Nature Publishing Group UK 2022-09-07 /pmc/articles/PMC9448807/ /pubmed/36068203 http://dx.doi.org/10.1038/s41392-022-01127-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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
Tobacco carcinogen induces tryptophan metabolism and immune suppression via induction of indoleamine 2,3-dioxygenase 1
title Tobacco carcinogen induces tryptophan metabolism and immune suppression via induction of indoleamine 2,3-dioxygenase 1
title_full Tobacco carcinogen induces tryptophan metabolism and immune suppression via induction of indoleamine 2,3-dioxygenase 1
title_fullStr Tobacco carcinogen induces tryptophan metabolism and immune suppression via induction of indoleamine 2,3-dioxygenase 1
title_full_unstemmed Tobacco carcinogen induces tryptophan metabolism and immune suppression via induction of indoleamine 2,3-dioxygenase 1
title_short Tobacco carcinogen induces tryptophan metabolism and immune suppression via induction of indoleamine 2,3-dioxygenase 1
title_sort tobacco carcinogen induces tryptophan metabolism and immune suppression via induction of indoleamine 2,3-dioxygenase 1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9448807/
https://www.ncbi.nlm.nih.gov/pubmed/36068203
http://dx.doi.org/10.1038/s41392-022-01127-3
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