活性氧对肿瘤免疫检查点的调控作用及机制研究进展  

Research progress on the regulation and mechanism of reactive oxygen species on tumor immune checkpoints

作　　者：李晓风 王圆 韦淑颖 邹伟 罗欣 李佳怡 韦忠红[2] 余苏云[2] 李晓曼 陈文星[2] 王爱云[2] 赵杨[1] 陆茵[2,3,4] 吴媛媛 LI Xiao-feng;WANG Yuan;WEI Shu-ying;ZOU Wei;LUO Xin;LI Jia-yi;WEI Zhong-hong;YU Su-yun;LI Xiao-man;CHEN Wen-xing;WANG Ai-yun;ZHAO Yang;LU Yin;WU Yuan-yuan(School of Medicine and Holistic Integrative Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,China;Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica,School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China;Jiangsu International Cooperative Laboratory of Traditional Chinese Medicine and Regenerative Medicine Research,Nanjing University of Chinese Medicine,Nanjing 210023,China;Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor,Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]南京中医药大学,整合医学学院,江苏南京210023 [2]南京中医药大学药学院,江苏省中药药效与安全性评价重点实验室,江苏南京210023 [3]南京中医药大学,江苏省中医药与再生医学研究国际合作联合实验室,江苏南京210023 [4]南京中医药大学,江苏省中医药防治肿瘤协同创新中心,江苏南京210023

出　　处：《药学学报》2022年第6期1565-1573,共9页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81961128020);南京中医药大学中药学一流学科开放课题(2020YLXK20);江苏省研究生实践创新计划(SJCX22_0783)。

摘　　要：免疫检查点(immune checkpoints,ICs)是一类在免疫细胞上表达的免疫抑制性分子,能调节免疫激活程度。免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)可阻断免疫检查点与其配体结合,抑制肿瘤免疫逃逸作用,提高免疫系统对肿瘤细胞的杀伤作用,逐渐成为肿瘤治疗的一种常规策略。然而,响应率低与耐药性的产生严重影响了免疫检查点抑制剂的临床疗效。活性氧(reactive oxygen species,ROS)是一类性质活泼的氧的电子还原产物,也是细胞代谢的天然副产物,可作为细胞间信号传递的调节分子。肿瘤微环境(tumor microenvironment,TME)常处于氧化应激(oxidative stress,OS)状态,即氧化系统与抗氧化系统之间的失衡状态。存在于TME中的ROS可通过调节肿瘤免疫检查点的表达及活性,影响免疫检查点与其配体之间的相互作用,进而影响免疫细胞的抗肿瘤作用。越来越多的研究表明,ROS可通过多种途径调控肿瘤免疫检查点。因此,选择合适的ROS调节剂与免疫检查点抑制剂联合用药,可为肿瘤免疫发挥协同增效作用。本文就ROS的共同代谢来源、特性、ROS对肿瘤免疫检查点的调控作用和机制及治疗应用进行综述。Immune checkpoints(ICs)are immunosuppressive molecules expressed on immune cells,which can regulate immune cells’activation.Immune checkpoint inhibitors(ICIs)which can block the interaction of immune checkpoints and their ligands,improve the cytotoxic effect of the immune system on tumor cells.Immunotherapy such as employing ICIs has gradually become a conventional therapeutic strategy for cancer treatment.However,the low response rate and the emergence of drug resistance have seriously affected the clinical efficacy of ICIs.Reactive oxygen species(ROS)are electronic reduction products of active oxygen,as well as natural by-products of cell metabolism,which can be used as regulators of intercellular signals.Tumor microenvironment(TME)is often in the state of oxidative stress(OS),which is the imbalance between oxidative system and antioxidant system.ROS can affect the interaction with its ligands by regulating the expression and activity of immune checkpoints in TME,thus affecting the anti-tumor effect of immune cells.Accumulating studies have shown that ROS could regulate tumor immune checkpoints through several pathways.Due to different types and stages of tumor,it would be clinical beneficial to understand the mechanistic link of ROS on tumor immune checkpoint,and choose appropriate ROS regulators combined with immune checkpoint inhibitors to maximize anti-tumor effects.This article reviews the common metabolic sources and characteristics of ROS,the regulatory effect and mechanism of ROS on tumor immune checkpoints and its therapeutic application.

关 键 词：活性氧 氧化应激 免疫检查点 肿瘤微环境 作用机制 

分 类 号：R966[医药卫生—药理学]