Yang T, Li QQ, Liu YM, Yang B. T cells in pancreatic cancer stroma: Tryptophan metabolism plays an important role in immunoregulation. World J Gastroenterol 2023; 29(17): 2701-2703 [PMID: 37213408 DOI: 10.3748/wjg.v29.i17.2701]
Corresponding Author of This Article
Biao Yang, MD, PhD, Professor, Surgeon, Teacher, Department of Abdominal Oncology, Division of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, Sichuan Province, China. landayb@163.com
Research Domain of This Article
Immunology
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. May 7, 2023; 29(17): 2701-2703 Published online May 7, 2023. doi: 10.3748/wjg.v29.i17.2701
T cells in pancreatic cancer stroma: Tryptophan metabolism plays an important role in immunoregulation
Ting Yang, Qiao-Qi Li, Yong-Mei Liu, Biao Yang
Ting Yang, Qiao-Qi Li, Biao Yang, Department of Abdominal Oncology, Division of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Yong-Mei Liu, Division of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Yang T, Li QQ, Liu YM, and Yang B designed the research study; Yang T and Li QQ performed the research; Yang T, Li QQ, and Yang B analyzed the data and wrote the manuscript; All authors read and approved the final manuscript.
Supported byNational Natural Science Foundation of China, No. 82200695.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Biao Yang, MD, PhD, Professor, Surgeon, Teacher, Department of Abdominal Oncology, Division of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, Sichuan Province, China. landayb@163.com
Received: December 7, 2022 Peer-review started: December 7, 2022 First decision: January 22, 2023 Revised: February 10, 2023 Accepted: April 4, 2023 Article in press: April 4, 2023 Published online: May 7, 2023
Abstract
Several studies have shown that the immune system is highly regulated by tryptophan metabolism, which serves as an immunomodulatory factor. The indoleamine 2,3-dioxygenase 1 (IDO1), as an intracellular enzyme that participates in metabolism of the essential amino acid tryptophan in the kynurenine pathway, is an independent prognostic marker for pancreatic cancer (PC). First, overexpression of IDO1 inhibits the maturation of dendritic cells and T-cell proliferation in the liver and spleen. Second, the high expression of kynurenine induces and activates the aryl hydrocarbon receptor, resulting in upregulated programmed cell death protein 1 expression. Third, the induction of IDO1 can lead to loss of the T helper 17 cell/regulatory T cell balance, mediated by the proximal tryptophan catabolite from IDO metabolism. In our study, we found that overexpression of IDO1 upregulated CD8+ T cells and reduced natural killer T cells in pancreatic carcinoma in mice. Hence, it may be essential to pay more attention to tryptophan metabolism in patients, especially those who are tolerant to immunotherapy for PC.
Core Tip: There are numerous lines for evidence for tryptophan metabolism, which serves as an immunomodulatory factor. Indoleamine2,3-dioxygenase1 (IDO1) overexpression inhibits the maturation of dendritic cells and T-cell proliferation in the spleen. The high expression of kynurenine induces and activates the aryl hydrocarbon receptor, resulting in upregulated programmed cell death protein 1 expression. The induction of IDO1 can lead to loss of T helper 17 cell/regulatory T cell balance. We also found that overexpression of IDO1 upregulated CD8+ T cells and reduced natural killer T cells in PC in mice.
