Wang Jinli, Xing Lumin
Department of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC, USA.
The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China.
Cell Biol Int. 2025 Feb;49(2):129-138. doi: 10.1002/cbin.12263. Epub 2024 Dec 8.
The presence of DNA in the cytosol triggers a protective response from the innate immune system. Cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) is an essential cytosolic DNA sensor that triggers a potent innate immune response. As a result of this signaling cascade reaction, type I interferon and other immune mediators activate an immune response. The cGAS-STING pathway has great anticancer immunity-boosting potential since it produces type I interferons. The detection of double-stranded DNA (dsDNA) in response to various stimuli initiates a protective host's cGAS-STING signals. So, it is clear that a substantial relationship is expected between cancer biotherapy and the functioning of the cGAS-STING pathway. Several STING agonists with promising outcomes have been created for preclinical cancer therapy research. Notably, immunotherapy has dramatically extended patient survival and radically altered the course of lung cancer treatment, particularly in more advanced instances. However, this method is still ineffective for a large number of lung cancer patients. cGAS-STING can overcome resistance and boost anticancer immunity by stimulating the activity of many pro-inflammatory mediators, augmenting dendritic cell cross-presentation, and initiating a tumor-specific CD8 T cell response. This review aims to present the most recent results on the functionality of the cGAS-STING pathway in cancer progression and its potential as an immunotherapy target, with a focus on lung cancer.
细胞质中DNA的存在会触发先天性免疫系统的保护性反应。环磷酸鸟苷-腺苷合成酶-干扰素基因刺激物（cGAS-STING）是一种重要的细胞质DNA传感器，可触发强大的先天性免疫反应。作为这种信号级联反应的结果，I型干扰素和其他免疫介质会激活免疫反应。由于cGAS-STING途径能产生I型干扰素，因此它具有巨大的抗癌免疫增强潜力。对各种刺激作出反应时检测到双链DNA（dsDNA）会启动宿主的保护性cGAS-STING信号。所以，很明显癌症生物疗法与cGAS-STING途径的功能之间存在密切关系。已经开发出几种在临床前癌症治疗研究中具有良好效果的STING激动剂。值得注意的是，免疫疗法显著延长了患者的生存期，并从根本上改变了肺癌的治疗进程，尤其是在病情更严重的情况下。然而，这种方法对大量肺癌患者仍然无效。cGAS-STING可以通过刺激多种促炎介质的活性、增强树突状细胞的交叉呈递以及引发肿瘤特异性CD8 T细胞反应来克服耐药性并增强抗癌免疫力。本综述旨在介绍cGAS-STING途径在癌症进展中的功能及其作为免疫治疗靶点的潜力的最新研究成果，重点关注肺癌。
