Fig. 3.

Role of STING pathway in tumor suppression. a cGAS-STING pathway and cancer-immunity cycle. cGAS-STING pathway functions as a tumor suppressor induced by DNA damage. Cytosolic DNA generated from different sources of DNA damage could be sensed by enzyme cGAS in a tumor cell. The cGAS then activates STING to upregulate type I IFN expression, which mediates tumor-suppressive effects. In addition, the cGAS-STING signaling allows the crosstalk between the tumor cells and immune cells nearby. Tumor-derived cGAMP or tumor-derived DNA could activate the activation of DCs, which activates the cGAS-STING pathway and promote immune cells against tumors. b cGAS-STING in innate immune sensing and spontaneous anti-tumor T cell responses. Tumor-derived DNA can induce cGAS-STING pathway activation of APCs and upregulate expression of type I IFNs, which increases its lymph node-homing capability and spontaneous T cells. Abbreviations: cGAMP, 2′,3′-cyclic GMP-AMP; CTL, cytotoxic T lymphocytes; IFN, interferon; NK cells, natural killer cells; SASP, senescence-associated secretory phenotype; TME, tumor microenvironment