Insight into the dichotomous regulation of STING activation in immunotherapy

Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway (cGAS-STING) is a hub linking innate immunity and adaptive immunity against pathogen infection by inducing the production of type I interferon (IFN-I). It also plays pivotal roles in modulating tumorigenesis by ensuring the antigen presentation, T cell priming, activation, and tumor regression. Given its antitumor immune properties, cGAS-STING has attracted intense focus and several STING agonists have entered into clinical trials. However, some problems still exist when activating STING for use in oncological indications. It is remarkable that multiple downstream cytokines such as TNF-α, IL-6 may lead to inflammatory disease and even tumor metastasis in practical trials. Besides, there is a synergistic effect when STING agonists are combined with other immunotherapies. In this review, we discussed the advanced understanding between STING and anti-tumor immunity, as well as a variety of promising clinical treatment strategies.