DOI: 10.1515/mr-2023-0061
The multiple faces of cGAS-STING in antitumor immunity:prospects and challenges
Zheqi Zhou1
Sanling Huang1
Fangying Fan2
Yan Xu1
Casey Moore3
Sirui Li4
Chuanhui Han5
1.Peking University International Cancer Institute,Peking University Cancer Hospital and Institute,Health Science Center,Peking University,Beijing,China2.Department of Interventional Ultrasound,Chinese PLA General Hospital,Beijing,China3.Departments of Immunology,Pathology,UT Southwestern Medical Center,Dallas,Texas,USA4.Department of Genetics,Lineberger Comprehensive Cancer Center,University of North Carolina at Chapel Hill,Chapel Hill,NC 27599,USA5.Peking University International Cancer Institute,Peking University Cancer Hospital and Institute,Health Science Center,Peking University,Beijing 100143,China
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 im-munity.Recent evidence show that several antitumor ther-apies,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 in-dustry.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-Ⅰsignaling,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.
机标关键词：antitumorcgas-stingchallengesfacesimmunitymultipleprospects
论文发表日期：2024-06-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：19( 173-191 )
英文信息