基于cGAS/STING信号通路的肿瘤治疗研究进展

Advances in tumor treatment research based on cGAS/STING signaling pathway

  • 摘要: 先天免疫是保护机体免受疾病侵害的第一道防线。近年来,一系列研究表明宿主先天免疫的重要组成成分cGAS/STING信号通路可能在抗肿瘤免疫中发挥重要作用。cGAS是一种先天免疫传感器,可识别胞质异常dsDNA,通过催化第二信使cGAMP的形成,STING蛋白得以激活,从而促进Ⅰ型干扰素的释放。所产生的Ⅰ型干扰素可以通过促进树突状细胞的成熟和迁移、增强T淋巴细胞或自然杀伤细胞的细胞毒性效应,有效地连接先天免疫和适应性免疫。cGAS/STING信号通路被证实在肿瘤的发生和进展中,除了具有抗肿瘤效应,还具有一定的促瘤作用。随着STING激动剂进入各项研究试验中,其与各种治疗方式的联合应用被人们广泛研究,同时人们也开发了纳米载药体系来实现STING激动剂更强的抗肿瘤作用。本文将对cGAS/STING信号通路调节肿瘤的机制及其在免疫治疗中的应用进行综述,为开发靶向该通路的免疫治疗提供依据。

     

    Abstract: Innate immunity is the body's first line of defense against disease. In recent years, a series of studies have shown that the cGAS/STING signaling pathway, an important component of host innate immunity, may play an important role in anti-tumor immunity. cGAS is an innate immune sensor that can recognize abnormal dsDNA in the cytoplasm and activate the STING protein by catalyzing the formation of the second messenger cGAMP, thereby promoting the release of type Ⅰ interferon. The produced type Ⅰ interferon can effectively connect innate immunity and adaptive immunity by promoting the maturation and migration of dendritic cells and enhancing the cytotoxic effect of T lymphocytes or natural killer cells. The cGAS/STING signaling pathway has been confirmed to have anti-tumor effects as well as tumor-promoting effects in the occurrence and progression of tumors. STING agonists have entered clinical trials, and combinations with various treatment modes have also been widely studied. At the same time, nano-drug loading systems have also been developed to achieve stronger anti-tumor effects of STING agonists. This article will review the mechanism of tumor regulation and its application in immunotherapy, so as to provide reference for the development of immunotherapy targeting this pathway.

     

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