张弛, 严时佳, 万国辉. 色氨酸与肿瘤免疫J. 药学学报, 2022, 57(9): 2580-2589. DOI: 10.16438/j.0513-4870.2022-0528
引用本文: 张弛, 严时佳, 万国辉. 色氨酸与肿瘤免疫J. 药学学报, 2022, 57(9): 2580-2589. DOI: 10.16438/j.0513-4870.2022-0528
ZHANG Chi, YAN Shi-jia, WAN Guo-hui. Tryptophan and tumor immunityJ. Acta Pharmaceutica Sinica, 2022, 57(9): 2580-2589. DOI: 10.16438/j.0513-4870.2022-0528
Citation: ZHANG Chi, YAN Shi-jia, WAN Guo-hui. Tryptophan and tumor immunityJ. Acta Pharmaceutica Sinica, 2022, 57(9): 2580-2589. DOI: 10.16438/j.0513-4870.2022-0528

色氨酸与肿瘤免疫

Tryptophan and tumor immunity

  • 摘要: 色氨酸(tryptophan, Trp) 作为人体必需氨基酸, 生理功能多样, 在肿瘤的代谢过程中具有重要意义。在人体中, 色氨酸主要经犬尿氨酸代谢, 既促进肿瘤细胞固有的恶性特性, 又限制肿瘤免疫, 因此它是癌症免疫治疗的重要药物开发靶点。肿瘤中色氨酸代谢的改变常伴随色氨酸相关酶基因表达的异常, 其中以吲哚胺2, 3-双加氧酶(indoleamine 2, 3-bioxygenase, IDO) 相关基因表达和色氨酸2, 3-双加氧酶(tryptophan 2, 3-dioxygenase, TDO) 相关基因改变最为常见。基于此, IDO抑制剂、TDO抑制剂及联合治疗被应用于大量的临床试验中。本文从色氨酸代谢出发, 阐述肿瘤中犬尿氨酸代谢途径、肿瘤细胞IDO、TDO、犬尿氨酸(kynurenine, KYN) 相关基因的表达调控, 并概述色氨酸相关肿瘤治疗方案的新进展, 为肿瘤治疗方案的进一步探索提供新思路。

     

    Abstract: As an essential amino acid, tryptophan (Trp) has various physiological functions and is of great significance in the metabolic process of tumors. In the human body, tryptophan is mainly transformed through kynurenine metabolic pathway, which not only promotes the inherent malignant properties of tumor cells, but also leads to immune-suppressive tumor microenvironment. Changes in tryptophan metabolism often occur in tumors, accompanied by abnormal gene expression of tryptophan-related enzymes, among which indoleamine 2, 3-bioxygenase (IDO)-related gene expression and tryptophan 2, 3-dioxygenase (TDO)-related gene changes are the most significant. A large number of clinical trials on IDO inhibitors, TDO inhibitors and combination therapy have been carried out. This paper reviewed the tryptophan metabolic pathway, regulation of IDO (TDO), kynurenine (KYN) and other related genes in tumor cells, and outlined the development of therapeutic schedule targeting tryptophan-related genes. The new progress provides new ideas for the further exploration of tumor treatment options.

     

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