cGAS-STING信号通路在肿瘤治疗中的作用与应用前景  

The role and application prospect of cGAS-STING signaling pathway in tumor treatment

作　　者：高燕萍 蒋雪萍 刘星煜 陈佳蕊 龚 谢丛华[1] Gao Yanping;Jiang Xueping;Liu Xingyu;Chen Jiarui;Gong Yan;Xie Conghua(Department of Radiation and Medical Oncology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China;Department of Biological Repositories,Zhongnan Hospital of Wuhan University,Wuhan 430071,China)

机构地区：[1]武汉大学中南医院肿瘤放化疗科,430071 [2]武汉大学中南医院生物样本库,430071

出　　处：《中华放射肿瘤学杂志》2021年第5期518-522,共5页Chinese Journal of Radiation Oncology

基　　金：国家自然科学基金(81572967、81773236);国家疑难病症诊治中心(肿瘤),国家临床重点专科([2013]544);湖北省卫生健康委员会联合基金重点项目(WJ2019h002)。

摘　　要：肿瘤免疫疗法通过调节先天免疫和适应性免疫系统来对抗肿瘤。环鸟苷酸-腺苷合成酶(cGAS)是外源性和内源性DNA先天免疫应答的关键调节因子。cGAS识别胞质DNA后,产生第二信使cGAMP,随后与激活干扰素调节因子3接头蛋白STING(也被称为MITA、MPYS和ERIS)结合诱导产生Ⅰ型干扰素和炎性细胞因子来介导抗先天免疫。最近的研究阐释了该通路能被来自肿瘤自身的DNA和基因组不稳定性副产物激活并影响肿瘤发生发展,在天然抗肿瘤免疫及免疫检查点阻滞治疗中起关键作用。本综述概述了在肿瘤中对cGAS-STING信号通路的认识,强调了其在肿瘤免疫和放疗中的重要作用,以及针对该通路的潜在靶向或替代治疗方法。Novel cancer immunotherapy can treat tumors through regulating innate immunity and adaptive immune system.cGMP-AMP synthase(cGAS)is a key regulator of innate immune response to both exogenous and endogenous DNA.After recognizing the cytoplasmic DNA,cGAS produces the second messenger cyclic GMP-AMP(cGAMP),which subsequently combines with the adaptor STING(also known as MITA,MPYS and ERIS)to mediate innate immunity by inducing the production of type I interferons and inflammatory cytokines.Recent studies have revealed that the cGAS/STING signaling pathway can be activated by tumor-derived DNA and by-products of genomic instability and affect the incidence and development of tumors,which plays a critical role in the natural antitumor immunity across cancer types and immune checkpoint blockade therapy.In this article,current understanding of cGAS/STING signaling pathway in tumors was summarized,the pivotal role in tumor immunity and radiotherapy was highlighted,and the potential targeted or alternative therapy of this signaling pathway was reviewed.

关 键 词：cGAS基因 STING基因 信号通路 肿瘤/放射免疫疗法 

分 类 号：R730.5[医药卫生—肿瘤]