IDO与肿瘤免疫逃逸研究进展.docVIP

IDO与肿瘤免疫逃逸研究进展 贾云泷，王郁，刘丽华 河北医科大学第四医院 生物治疗科 河北 石家庄 050035 按下述格式补充： [基金项目] 国家自然科学基金资助项目（No.No。Project supported by the National Natural Science Foundation of China (No.No. [作者简介]（只介绍第一作者）黄邵洪（1976-），男，福建省福州市人，博士，主要从事胸部肿瘤基础及临床研究。E-mail:legendhuang@126.com [通信作者]叶升（Ye Sheng，corresponding author），E-mail: ye163.com 【摘要】：吲哚胺2,3-双加氧酶（Indoleamine 2,3-dioxygenase, IDO）是一种免疫调节酶，调节性T细胞在肿瘤的免疫逃逸中重要作用肿瘤细胞肿瘤微环境IDO的可以被其竞争性抑制剂1-甲基色氨酸（1-methyl-tryptophan, 1-MT）所，其异构体D-1-MT在临床试验中可以干扰肿瘤细胞的免疫逃逸，显著增强放疗、化疗和免疫治疗的疗效，有望成为一种新的抗肿瘤药物。 【关键词】：IDO；免疫逃逸；免疫治疗Advances of IDO in Tumor Immune Escape Yunlong Jia, Yu Wang, Lihua Liu Department of Biotherapy, The Fourth Hospital of Hebei Medical University, Hebei Province Shijiazhuang, 050035, China [Abstract]: Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme which can suppress anti-tumor immune response. IDO anticipates tumor immune escape through various pathways including inducing effector T cells anergy and natural killer (NK) cells dysfunction, forming a positive feedback circle with regulatory T cells (Tregs). Tumor cells are competent to recruit dendrtitic cells (DC) expressing IDO into the microenvironment to escape from immune surveillance, thus DC with high level of IDO can be found in tumor infiltrating tissues and draining lymph nodes. 1-methyl-tryptophan (1-MT), can reverse IDO’s immunosuppressive influence as IDO’s competitive inhibitor, and its isomer D-1-MT has shown its efficacy when synergizing with radiotherapy, chemotherapy and immunotherapy in clinical trial, which might be a new promising anti-tumor therapy. [Key Words]: IDO; T cell; NK cell; immune escape; immunotherapy 吲哚胺2,3-双加氧酶indoleamine 2,3-dioxygenase, IDO）是机体内一种免疫调节酶，。肿瘤细胞利用这种负向的免疫调节在肿瘤浸润组织和肿瘤引流淋巴结（tumor-draining lymph node, TDLN）中均存在高水平表达的IDO，且IDO表达水平与患者预后呈的负相关关系[1, 2]， IDO的高表达在临床上可以作为肿瘤预后不良的指标。IDO与肿瘤免疫逃逸的关系是肿瘤学的研究热点之一。本文就近年来IDO与肿瘤免疫逃逸的研究进展作一综述。 IDO的生物学特性 IDO是肝脏以外唯一可催化色氨酸分子氧化裂解使其沿犬尿途径分解代谢的限速酶，正常机体内主要分布于胸腺髓质和次级淋