The multiple faces of cGAS-STING in antitumor immunity:prospects and challenges  

作　　者：Zheqi Zhou Sanling Huang Fangying Fan Yan Xu Casey Moore Sirui Li Chuanhui Han 

机构地区：[1]Peking University International Cancer Institute,Peking University Cancer Hospital and Institute,Health Science Center,Peking University,Beijing,China [2]Department of Interventional Ultrasound,Chinese PLA General Hospital,Beijing,China [3]Departments of Immunology,Pathology,UT Southwestern Medical Center,Dallas,Texas,USA [4]Peking University International Cancer Institute,Peking University Cancer Hospital and Institute,Health Science Center,Peking University,Beijing 100143,China [5]Department of Genetics,Lineberger Comprehensive Cancer Center,University of North Carolina at Chapel Hill,Chapel Hill,NC 27599,USA

出　　处：《Medical Review》2024年第3期173-191,共19页医学评论（英文）

基　　金：supported by National Key Research and Development Program of China 2023YFC3404600;National Natural Science Foundation of China grant(82371848)。

摘　　要：As a key sensor of double-stranded DNA(dsDNA),cyclic GMP-AMP synthase(cGAS)detects cytosolic dsDNA and initiates the synthesis of 2′3′cyclic GMP-AMP(cGAMP)that activates the stimulator of interferon genes(STING).This finally promotes the production of type I interferons(IFN-I)that is crucial for bridging innate and adaptive immunity.Recent evidence show that several antitumor therapies,including radiotherapy(RT),chemotherapy,targeted therapies and immunotherapies,activate the cGAS-STING pathway to provoke the antitumor immunity.In the last decade,the development of STING agonists has been a major focus in both basic research and the pharmaceutical industry.However,up to now,none of STING agonists have been approved for clinical use.Considering the broad expression of STING in whole body and the direct lethal effect of STING agonists on immune cells in the draining lymph node(dLN),research on the optimal way to activate STING in tumor microenvironment(TME)appears to be a promising direction.Moreover,besides enhancing IFN-I signaling,the cGAS-STING pathway also plays roles in senescence,autophagy,apoptosis,mitotic arrest,and DNA repair,contributing to tumor development and metastasis.In this review,we summarize the recent advances on cGAS-STING pathway’s response to antitumor therapies and the strategies involving this pathway for tumor treatment.

关 键 词：cGAS STING agonist IFN-I TUMOR 

分 类 号：R730.3[医药卫生—肿瘤]