Indoleamine 2,3-dioxygenase-1 involves in CD8 + T cell exhaustion in glioblastoma via regulating tryptophan levels.

Autor: Zhou Y; School of Basic Medicine, Jinzhou Medical University, Jinzhou, Liaoning Province, China., Yao L; School of Basic Medicine, Jinzhou Medical University, Jinzhou, Liaoning Province, China., Ma T; Institution of Life Science, Jinzhou Medical University, Jinzhou, China., Wang Z; Institution of Life Science, Jinzhou Medical University, Jinzhou, China., Yin Y; Institution of Life Science, Jinzhou Medical University, Jinzhou, China., Yang J; School of Basic Medicine, Jinzhou Medical University, Jinzhou, Liaoning Province, China., Zhang X; School of Basic Medicine, Jinzhou Medical University, Jinzhou, Liaoning Province, China., Zhang M; Institution of Life Science, Jinzhou Medical University, Jinzhou, China., Qin G; School of Basic Medicine, Jinzhou Medical University, Jinzhou, Liaoning Province, China., Ma J; School of Basic Medicine, Jinzhou Medical University, Jinzhou, Liaoning Province, China., Zhao L; Collaborative Innovation Center for Age-related Disease, Life Science Institute of Jinzhou Medical University, Jinzhou 121001, Liaoning, China., Liang J; Collaborative Innovation Center for Age-related Disease, Life Science Institute of Jinzhou Medical University, Jinzhou 121001, Liaoning, China; Liaoning Provincial Key Laboratory of Neurodegenerative Diseases and Department of Neurobiology, Jinzhou Medical University, China. Electronic address: liangjia@jzmu.edu.cn., Zhang J; Liaoning Technology and Engineering Center for Tumor Immunology and Molecular Theranostics, Collaborative Innovation Center for Age-related Disease, Life Science Institute of Jinzhou Medical University, Jinzhou 121001, Liaoning, China. Electronic address: jinyizhang688@163.com.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 05; Vol. 142 (Pt A), pp. 113062. Date of Electronic Publication: 2024 Sep 07.
DOI: 10.1016/j.intimp.2024.113062
Abstrakt: Indoleamine 2,3-dioxygenase-1 (IDO-1) is an enzyme that catalyzes the metabolism of tryptophan (Trp). It is expressed in limited amounts in normal tissues but significantly upregulated during inflammation and infection. Various inflammatory factors, especially IFN-γ, can induce the expression of IDO-1. While extensive research has been conducted on the role of IDO-1 in tumors, its specific role in complex central nervous system tumors such as glioblastoma (GBM) remains unclear. This study aims to explore the role of IDO-1 in the development of GBM and analyze its association with tryptophan levels and CD8 + T cell exhaustion in the tumor region. To achieve this, we constructed an orthotopic mouse glioblastoma tumor model to investigate the specific mechanisms between IDO-1, GBM, and CD8 + T cell exhaustion. Our results showed that IDO-1 can promote CD8 + T cell exhaustion by reducing tryptophan levels. When IDO-1 was knocked down in glioblastoma cells, other cells within the tumor microenvironment upregulated IDO-1 expression to compensate for the loss and enhance immunosuppressive effects. Therefore, the data suggest that the GBM microenvironment controls tryptophan levels by regulating IDO-1 expression, which plays a critical role in immune suppression. These findings support the use of immune therapy in combination with IDO-1 inhibitors or tryptophan supplementation as a potential treatment strategy.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: