肿瘤免疫微环境中cGAS-STING信号通路的细胞间信号传递
Cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment
王梦秋 1徐平龙 2吴芑柔1
作者信息
- 1. 浙江大学生命科学研究院,浙江 杭州 310058
- 2. 浙江大学生命科学研究院,浙江 杭州 310058;浙江大学生命系统稳态与保护教育部重点实验室 浙江省癌症分子细胞生物学重点实验室,浙江 杭州 310058;浙江大学杭州国际科创中心智能医药研究所,浙江 杭州 311200;浙江大学癌症研究院,浙江 杭州 310058
- 折叠
摘要
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.
Abstract
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.
关键词
肿瘤微环境/环鸟苷酸-腺苷酸合成酶-干扰素基因刺激因子/细胞间信号传递/双链DNA/肿瘤免疫/免疫应答/综述Key words
Tumor microenvironment/cGAS-STING/Cell-to-cell communication/Double stranded DNA/Tumor immunity/Immune responses/Review引用本文复制引用
基金项目
国家自然科学基金(31725017)
国家自然科学基金(31830052)
国家重点研发计划(2021YFA1301401)
出版年
2024
NETL
NSTL
维普
万方数据