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Role of tryptophan metabolism in cancers and therapeutic implications.

Authors
  • Liu, Xiao-Han1
  • Zhai, Xiao-Yue2
  • 1 Department of Histology and Embryology, Basic Medical College, China Medical University, Shenyang, Liaoning, 110122, China. , (China)
  • 2 Department of Histology and Embryology, Basic Medical College, China Medical University, Shenyang, Liaoning, 110122, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Biochimie
Publication Date
Jan 16, 2021
Volume
182
Pages
131–139
Identifiers
DOI: 10.1016/j.biochi.2021.01.005
PMID: 33460767
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Tryptophan (Trp) metabolism is associated with diverse biological processes, including nerve conduction, inflammation, and the immune response. The majority of free Trp is broken down through the kynurenine (Kyn) pathway (KP), in which indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO) catalyze the rate-limiting step. Clinical studies have demonstrated that Trp metabolism promotes tumor progression due to modulation of the immunosuppressive microenvironment through multiple mechanisms. In this process, IDO-expressing dendritic cells (DCs) exhibit tolerogenic potential and orchestrate T cell immune responses. Various signaling molecules control IDO expression, initiating the immunoregulatory pathway of Trp catabolism. Based on these characteristics, KP enzymes and catabolites are emerging as significant prognostic indicators and potential therapeutic targets of cancer. The physiological and oncologic roles of Trp metabolism are briefly summarized here, along with great challenges for treatment strategies. Copyright © 2021. Published by Elsevier B.V.

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