吲哚胺2,3-双加氧酶与肿瘤免疫耐受  

Indoleamine 2,3-dioxygenase and tumor immune tolerance

作　　者：张康平 张琪 于恺英 陈永兵 饶本强 石汉平 ZHANG Kang-ping;ZHANG Qi;YU Kai-ying;RAO Ben-qiang;SHI Han-ping(Department of Gastrointestinal Surgery,Beijing Shijitan Hospital,Capital Medical University/Department of Oncology,Capital Medical University,Beijing 100038,China)

机构地区：[1]首都医科大学附属北京世纪坛医院胃肠外科/首都医科大学肿瘤学系,北京100038

出　　处：《肿瘤代谢与营养电子杂志》2019年第4期505-510,共6页Electronic Journal of Metabolism and Nutrition of Cancer

基　　金：国家重点研发计划项目(2017YFC1309200)。

摘　　要：人体免疫系统可以对肿瘤表达的多种异常抗原产生免疫反应,但肿瘤通过复杂的进化过程所致的免疫耐受现象能够降低宿主针对肿瘤的自身免疫反应,使宿主无法通过免疫系统对肿瘤细胞作出免疫应答。因此该现象可导致肿瘤细胞逃避宿主的免疫监视以及免疫系统的攻击,从而使肿瘤细胞得以在人体内增殖和转移。IDO是细胞内催化L-色氨酸经犬尿氨酸途径进行分解代谢的关键酶,也是一种与免疫抑制相关的酶。IDO在多种病理生理过程中促进机体免疫耐受的发生,因此与肿瘤的发生发展有密切关系。大量研究发现,IDO作为一种重要的抑制性免疫检查点,在肿瘤患者中其酶活性的增加会促进肿瘤免疫耐受现象的建立。随着IDO介导肿瘤免疫耐受相关分子机制的发现与证实,IDO抑制剂也已成为肿瘤免疫疗法中的关键研究领域。本文重点阐明IDO发现的起源过程、在正常人体和肿瘤患者中的表达情况、调节色氨酸代谢等免疫调节功能以及IDO诱导TME中肿瘤免疫耐受建立的几种重要机制,包括色氨酸耗竭、激活芳香烃受体、诱导调节性T细胞扩增与活化以及募集和激活大量骨髓来源的抑制性细胞等机制,以便能够为今后的深入研究和IDO抑制剂的治疗应用提供更广阔的思维。The immune system of human has been described to be able to produce the immune response to multiple abnormal antigens by tumors.Nevertheless,the immune tolerance of tumors,which induced by complex evolutionary steps of tumors,can reduce the host's autoimmune response to tumors.Therefore,the phenomenon of immune tolerance may cause tumor to evade the host's immune surveillance and attacks from the host's immune effector cells.In turn,tumors have the opportunity to proliferate and metabolize in the body.Indoleamine 2,3-dioxygenase(IDO)is a key enzyme entailed in immunosuppression that promotes the development of immune tolerance in a variety of pathophysiological processes.A large number of studies have found that IDO is an important inhibitory immune checkpoint,and the increase of its activity in patients will promote the establishment of immune tolerance.This article reviews the origin,expression and function of IDO as well as the mechanisms by which IDO promotes the establishment of tumor immune tolerance.Hence,the present review provides a broader perspective for IDO's further research and application in cancer therapy.

关 键 词：吲哚胺2 3-双加氧酶 肿瘤 免疫耐受 

分 类 号：R730.3[医药卫生—肿瘤]