Emerging mechanisms and implications of c GAS-STING signaling in cancer immunotherapy strategies  

作　　者：Jiawen Zhang Sihui Yu Qiao Peng Ping Wang Lan Fang 

机构地区：[1]Tongji University Cancer Center,Shanghai Tenth People’s Hospital,School of Medicine,Tongji University,Shanghai 200072,China [2]Reproductive Medicine Center,Department of Obstetrics and Gynecology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 201620,China [3]Department of Obstetrics and Gynecology,Zhongshan Hospital,Fudan University,Shanghai 200032,China

出　　处：《Cancer Biology & Medicine》2024年第1期45-64,共20页癌症生物学与医学（英文版）

基　　金：the National Key Research and Development Program of China(Grant Nos.2022YFC3401500 and 2020YFA0803201 to P.W.,and 2021YFA1302200 to L.F.);the National Natural Science Foundation of China(Grant Nos.31830053,31920103007,and 82341028 to P.W.;82122056,82073153,and 31871398 to L.F.and 31900568 to P.W.);the Natural Science Foundation of Shanghai(Grant No.22ZR1450700 to Z.J.W.)。

摘　　要：The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel protecting against tumor incursion,is a key player.The cyclic GMP-AMP synthase(c GAS)and stimulator of interferon genes(STING)pathway has been found to be a linchpin of innate immunity:activation of this signaling pathway orchestrates the production of type I interferon(IFN-α/β),thus fostering the maturation,differentiation,and mobilization of immune effectors in the tumor microenvironment.Furthermore,STING activation facilitates the release and presentation of tumor antigens,and therefore is an attractive target for cancer immunotherapy.Current strategies to activate the STING pathway,including use of pharmacological agonists,have made substantial advancements,particularly when combined with immune checkpoint inhibitors.These approaches have shown promise in preclinical and clinical settings,by enhancing patient survival rates.This review describes the evolving understanding of the c GAS-STING pathway's involvement in tumor biology and therapy.Moreover,this review explores classical and non-classical STING agonists,providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies.Despite challenges and complexities,the c GAS-STING pathway,a promising avenue for enhancing cancer treatment efficacy,has the potential to revolutionize patient outcomes.

关 键 词：cGAS-STING pathway type I interferon cyclic dinucleotide STING agonist cancer immunotherapy 

分 类 号：R730.51[医药卫生—肿瘤]