Cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment

Targeting cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway is a promising strategy for tumor treatment. The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of a second messenger 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING. Notably, in tumor immune microenvironment, key components of cGAS-STING pathway are transferred among neighboring cells. The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity. The membrane-based system, including extracellular vesicles transport, phagocytosis and membrane fusion transmit dsDNA, cGAMP and activated STING, enhances the immune surveillance and inflammatory responses. The membrane proteins, including a specific protein channel and intercellular gap junctions, transfer cGAMP and dsDNA, which are crucial to regulate immune responses. The ligand-receptor interactions for interferon transmission amplifies the anti-tumor response. This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment, explores how these mechanisms modulate immunological processes and discusses potential interventions and immunotherapeutic strategies targeting these signaling cascades.环鸟苷酸-腺苷酸合成酶（cGAS）-干扰素基因刺激因子（STING）信号通路是肿瘤免疫治疗中备受关注的靶点。模式识别受体cGAS识别胞质双链DNA（dsDNA），生成第二信使2 ´ 3 ´-环鸟苷酸-腺苷酸（cGAMP），活化接头蛋白STING，介导干扰素和促炎性细胞因子的产生，从而促进肿瘤免疫。肿瘤免疫微环境中cGAS-STING通路的细胞间信号传递维持并增强天然免疫应答，推动适应性免疫的发展。基于膜系统的细胞外囊泡运输、吞噬作用和细胞膜融合传递dsDNA、cGAMP以及活化的STING蛋白，加强免疫监视和炎症应答。基于膜蛋白的缝隙连接、膜转运蛋白传递cGAMP和dsDNA对免疫调节至关重要。此外，配体-受体反应传递干扰素进一步放大抗肿瘤免疫反应。本文描述了肿瘤免疫微环境中cGAS-STING通路的细胞间信号传递及其调控，讨论这些机制如何影响和调节肿瘤免疫过程，以及针对这些信号传递机制的潜在干预和免疫治疗策略。.