《生命科学》 2023, 35(5): 576-582

靶向色氨酸降解酶在肿瘤免疫治疗中的研究进展

康　玲^1,2 , 姜凯龙^2,* , 李　佳^1,2,*

¹中国药科大学，南京 210000 ²中科中山药物创新研究院，中山 528400

摘　要：

免疫疗法为肿瘤患者带来了巨大希望。色氨酸作为人体必需氨基酸，在肿瘤免疫中具有重要意义。吲哚胺-2,3- 双加氧酶1 和2 (indoleamine-2,3-dioxygenase 1/2, IDO1/2)、色氨酸-2,3- 双加氧酶2 (tryptophan-2,3-dioxygenase 2, TDO2) 和白介素4 诱导蛋白1 (interleukin-4-induced-1, IL4I1) 是催化色氨酸降解的关键酶。研究表明靶向色氨酸降解酶能够恢复抗肿瘤免疫反应，并与其他免疫疗法( 如免疫检查点抑制剂) 具有协同作用，这给免疫肿瘤学领域带来了希望。然而，IDO1 抑制剂的临床试验却带来了令人失望的结果。本综述将讨论色氨酸降解酶及其抑制剂在肿瘤免疫治疗中的潜在效果和问题，并提出了可选的规避方法。

通讯作者：姜凯龙 , Email:jiangkailong@zidd.ac.cn 李　佳 , Email:jli@simm.ac.cn

Progress of targeting tryptophan-degrading enzymes in tumor immunotherapy

KANG Ling^1,2 , JIANG Kai-Long^2,* , LI Jia^1,2,*

¹China Pharmaceutical University, Nanjing 210000, China ²Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China

Abstract:

Immunotherapy has brought great hope to cancer patients. Tryptophan, as an essential amino acid, is of great significance in tumor immunity. Indoleamine-2,3- dioxygenase 1 and 2 (indoleamine-2,3-dioxygenase 1/2, IDO1/2), tryptophan-2,3-dioxygenase 2 (TDO2) and  interleukin-4-induced-1 (IL4I1) are the key enzymes that  catalyze tryptophan degradation. Researches showed that targeting tryptophan-degrading enzymes restored the  antitumor immune response and had synergistic effects with other immunotherapies, such as immune-checkpoint
inhibitors, offering hope in the field of immune-oncology. However, clinical trials of IDO1 inhibitors have yielded disappointing results. This review will discuss the  potential effects and problems of tryptophan degrading enzymes and their inhibitors in tumor immunotherapy, and some alternative methods to avoid these problems are proposed.

Communication Author：JIANG Kai-Long , Email:jiangkailong@zidd.ac.cn LI Jia , Email:jli@simm.ac.cn