Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
Institute of Clinical Pharmacology, Engineering Research Center for applied Technology of Pharmacogenomics of Ministry of Education, Central South University, Changsha, 410078, People's Republic of China.
Mol Cancer. 2020 Aug 27;19(1):133. doi: 10.1186/s12943-020-01250-1.
Cellular recognition of microbial DNA is an evolutionarily conserved mechanism by which the innate immune system detects pathogens. Cyclic GMP-AMP synthase (cGAS) and its downstream effector, stimulator of interferon genes (STING), are involved in mediating fundamental innate antimicrobial immunity by promoting the release of type I interferons (IFNs) and other inflammatory cytokines. Accumulating evidence suggests that the activation of the cGAS-STING axis is critical for antitumor immunity. The downstream cytokines regulated by cGAS-STING, especially type I IFNs, serve as bridges connecting innate immunity with adaptive immunity. Accordingly, a growing number of studies have focused on the synthesis and screening of STING pathway agonists. However, chronic STING activation may lead to a protumor phenotype in certain malignancies. Hence, the cGAS-STING signaling pathway must be orchestrated properly when STING agonists are used alone or in combination. In this review, we discuss the dichotomous roles of the cGAS-STING pathway in tumor development and the latest advances in the use of STING agonists.
细胞对微生物 DNA 的识别是一种进化上保守的机制，通过这种机制，先天免疫系统可以检测病原体。环鸟苷酸-腺苷酸合酶 (cGAS) 及其下游效应物干扰素基因刺激物 (STING) 通过促进 I 型干扰素 (IFNs) 和其他炎症细胞因子的释放，参与介导基本的先天抗微生物免疫。越来越多的证据表明，cGAS-STING 轴的激活对于抗肿瘤免疫至关重要。cGAS-STING 调节的下游细胞因子，特别是 I 型 IFNs，充当连接先天免疫与适应性免疫的桥梁。因此，越来越多的研究集中在 STING 途径激动剂的合成和筛选上。然而，慢性 STING 激活可能导致某些恶性肿瘤中出现促肿瘤表型。因此，当单独或联合使用 STING 激动剂时，必须对 cGAS-STING 信号通路进行适当的调控。在这篇综述中，我们讨论了 cGAS-STING 通路在肿瘤发展中的双重作用以及 STING 激动剂的最新进展。
