靶向肿瘤相关巨噬细胞药物的研究进展  

Research progress in drugs targeting tumor associated macrophage

作　　者：任利文 杨艺辉 李婉 张宜之 杨红 张森 许芳 郝悦 曹婉昕 杜冠华 王金华 REN Li-wen;YANG Yi-hui;LI Wan;ZHANG Yi-zhi;YANG Hong;ZHANG Sen;XU Fang;HAO Yue;CAO Wan-xin;DU Guan-hua;WANG Jin-hua(Key Laboratory of Drug Target Research and Drug Screen,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,北京市药物靶点研究与新药筛选重点实验室,北京100050

出　　处：《药学学报》2023年第12期3508-3518,共11页Acta Pharmaceutica Sinica

基　　金：北京市自然科学基金资助项目(7212157);中国医学科学院医学与健康科技创新工程(2021-I2M-1-029,2022-I2M-JB-011).

摘　　要：肿瘤严重威胁人类生命健康,近年来其发病率和死亡率在全球范围内迅速增加。肿瘤治疗药物经历了细胞毒疗法、靶向疗法和免疫疗法的发展,其中肿瘤免疫治疗已经成为近年来快速发展起来的新兴抗肿瘤疗法,但其也存在一些相关的不良反应。肿瘤微环境是由免疫细胞、肿瘤血管、成纤维细胞、细胞外基质等多种成分构成的复杂动态环境,肿瘤微环境显著影响免疫治疗的效果。肿瘤微环境中的巨噬细胞被称为肿瘤相关巨噬细胞,近年来越来越多的研究表明肿瘤相关巨噬细胞在肿瘤免疫调节中起着重要作用,特别是在肿瘤免疫监控及免疫逃逸等方面发挥关键调节作用。目前,越来越多针对肿瘤相关巨噬细胞的抗肿瘤免疫治疗策略正处于研发阶段。基于肿瘤相关巨噬细胞在肿瘤免疫微环境中的重要作用以及其可以作为肿瘤免疫治疗的潜在靶点,本文对肿瘤相关巨噬细胞的亚型与功能、肿瘤相关巨噬细胞在肿瘤中的主要作用,近年来靶向肿瘤相关巨噬细胞的抗肿瘤策略相关研究以及药物研发现状进行综述,以期为肿瘤免疫治疗提供新的思路。Tumor brings great threat to human public health.In recent years,incidence rate and mortality of tumor were rapidly increased in the world.Anti-tumor therapies have undergone the development of cytotoxic therapy,targeted therapy,and immunotherapy.Among them,tumor immunotherapy is rapidly developed and becomes an important anti-tumor therapy in recent years,although it also brings some related side effects.Tumor microenvironment(TME)is composed of immune cells,vascular vessels,fibroblasts,the extracellular matrix,etc.TME significantly affects the efficacy of immunotherapy.Macrophages in the TME are named as tumor associated macrophages(TAMs).Recently,increasing studies have shown that TAMs play an important role in the regulation of tumor immunity,especially in tumor immune surveillance and immune escape.Currently,more and more anti-tumor immunotherapy strategies targeting TAMs are at the development stage.Based on the important role of TAMs in the TME and their potential as therapeutic targets in tumor immunotherapy,we first reviewed the subtypes and functions of TAMs,as well as the roles of TAMs in tumors.Furthermore,we summarized the research progress on anti-tumor strategies targeting TAMs and the current status of drug targeting TAMs.The current review will provide new ideas and novel insights for tumor immunotherapy.

关 键 词：免疫治疗 肿瘤微环境 肿瘤相关巨噬细胞 药物靶点 

分 类 号：R966[医药卫生—药理学]