Department of Histology and Embryology, Basic Medical College, China Medical University, Shenyang, Liaoning, 110122, China.
Department of Histology and Embryology, Basic Medical College, China Medical University, Shenyang, Liaoning, 110122, China.
Biochimie. 2021 Mar;182:131-139. doi: 10.1016/j.biochi.2021.01.005. Epub 2021 Jan 16.
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.
色氨酸（Trp）代谢与多种生物过程相关，包括神经传导、炎症和免疫反应。大多数游离色氨酸通过犬尿氨酸（Kyn）途径（KP）分解，其中吲哚胺 2,3-双加氧酶（IDO）和色氨酸 2,3-双加氧酶（TDO）催化限速步骤。临床研究表明，色氨酸代谢通过多种机制调节免疫抑制微环境，从而促进肿瘤进展。在这个过程中，表达 IDO 的树突状细胞（DCs）表现出耐受性潜力，并协调 T 细胞免疫反应。各种信号分子控制 IDO 的表达，启动色氨酸分解的免疫调节途径。基于这些特性，KP 酶和代谢产物正在成为癌症的重要预后指标和潜在治疗靶点。本文简要总结了色氨酸代谢的生理和肿瘤学作用，以及治疗策略面临的巨大挑战。
