Cellular recognition of microbial DNA is an evolutionarily conserved mechanism by which the innate immune system detects pathogens. Cyclic GMP-AMP synthase (cGAS) and its downstream effector, stimulator of interferon genes (STING), are involved in mediating fundamental innate antimicrobial immunity by promoting the release of type I interferons (IFNs) and other inflammatory cytokines. Accumulating evidence suggests that the activation of the cGAS-STING axis is critical for antitumor immunity. The downstream cytokines regulated by cGAS-STING, especially type I IFNs, serve as bridges connecting innate immunity with adaptive immunity. Accordingly, a growing number of studies have focused on the synthesis and screening of STING pathway agonists. However, chronic STING activation may lead to a protumor phenotype in certain malignancies. Hence, the cGAS-STING signaling pathway must be orchestrated properly when STING agonists are used alone or in combination. In this review, we discuss the dichotomous roles of the cGAS-STING pathway in tumor development and the latest advances in the use of STING agonists.
【저자키워드】 Innate immunity, type I interferon, cancer development, cGAS-STING, STING agonists, Antitumor response, 【초록키워드】 adaptive, Immunity, interferon, cytokine, innate immune system, DNA, pathway, phenotype, Pathogens, type I IFNs, Inflammatory cytokines, signaling pathway, Critical, mechanism, IFNs, Evidence, Combination, microbial, Activation, malignancies, agonist, cyclic, downstream, agonists, detect, conserved, involved, regulated, antimicrobial immunity, 【제목키워드】 Immunotherapy, Signaling, Comprehensive,