cGAS-STING信号通路调节剂在免疫治疗中的研究进展

Research progress of cGAS-STING signaling pathway modulators in immunotherapy

环鸟嘌呤-腺嘌呤核苷酸合成酶(cGAS)-干扰素基因刺激蛋白(STING)信号通路感知细胞质中的异常双链DNA后,诱导Ⅰ型干扰素(IFN-Ⅰ)和促炎细胞因子表达,从而激活宿主的免疫应答,增强机体抗肿瘤免疫反应和抗病原体感染。但是,cGAS-STING信号通路的持续激活会驱动自身免疫性疾病、衰老相关炎症和神经退行性病变等疾病。本文阐述了cGAS-STING信号通路参与调控多种免疫相关性疾病发生发展的机制,重点回顾了STING激动剂、cGAS抑制剂以及STING抑制剂的研发进展,为cGAS-STING调节剂的研发提供更多理论参考。

Upon monitoring cytoplasmic aberrant double-stranded DNA,cGAS-STING signaling pathway induces the expression of type I interferons and pro-inflammatory cytokines,which activates the host immune response and enhances anti-tumor immune response and resistance to pathogen infection.However,sustained activation of the cGAS-STING signaling pathway drives diseases such as autoimmune diseases,aging-associated inflammation,and neurodegenerative pathologies.Herein,we describe the mechanism by which cGAS-STING signaling pathway participates in regulating the development of various immune-related diseases,with a particular review of the research and development progress of STING agonists,cGAS inhibitors,and STING inhibitors,aiming to provide some theoretical reference for the future development of cGAS-STING modulators.