基于CD47/信号调节蛋白α信号轴的肿瘤联合治疗策略

Combination therapy strategies for cancer based on CD47/signal regulatory proteinαsignaling axis

肿瘤细胞通过表达免疫检查点逃避机体免疫系统攻击,免疫检查点抑制剂则通过靶向这些免疫检查点阻断肿瘤细胞对免疫系统的抑制,促进机体抗肿瘤免疫反应,从而产生强大的抗肿瘤效果。CD47作为固有免疫系统的免疫检查点,在多种不同类型的恶性肿瘤细胞表面过表达,它通过与巨噬细胞表面的信号调节蛋白α(SIRPα)结合转导抑制信号,抑制巨噬细胞对肿瘤细胞的吞噬,进而使肿瘤细胞逃避机体固有免疫系统的监视和攻击。阻断CD47/SIRPα信号轴可以激活巨噬细胞对肿瘤细胞的吞噬作用,启动机体抗肿瘤免疫反应,但是由于复杂的肿瘤微环境,阻断免疫细胞上的单一信号通路只能产生有限或轻微的影响。此外,单独使用靶向CD47/SIRPα信号轴的药物治疗肿瘤响应率较低,并且可能存在较严重的不良反应。为了克服上述问题,提高抗肿瘤效果,将靶向CD47/SIRPα信号轴的药物与其他抗肿瘤疗法联合应用成为最有效的策略之一。本文综述了近年来关于CD47/SIRPα信号轴的研究进展和基于靶向CD47/SIRPα信号轴药物的联合治疗策略。

Tumor cells evade the body’s immune system by expressing immune checkpoints.By blocking these immune checkpoints,immune checkpoint inhibitors can promote anti-tumor immune response and elicit strong anti-tumor effects.As an innate immune checkpoint,CD47 is widely overexpressed in different malignant tumors.It assists tumor cells to evade immune surveillance and attack by interacting with signal regulatory proteinα(SIRPα)on macrophages to inhibit the phagocytosis of tumor cells by macrophages.Blocking CD47/SIRPαsignaling axis can activate the phagocytosis of macrophages on tumor cells and promote the anti-tumor immune response.However,due to the complex tumor microenvironment,blocking a single signaling pathway on immune cells only has limited or mild effects.Moreover,the tumor response rate is low with drug targeting the CD47/SIRPαsignaling axis alone and there are serious adverse reactions.In order to overcome these problems and improve the antitumor effect,combining drugs targeting the CD47/SIRPαsignaling axis with other anti-tumor therapies becomes one of the most effective strategies.This article reviews the recent research progress on the CD47/SIRPαsignaling axis and combination therapy strategies based on drugs targeting the CD47/SIRPαsignaling axis.