The cGAS-STING pathway is a promising target for cancer immunotherapy. By detecting tumor-derived DNA, cGAS can stimulate endogenous antitumor immunity. In preclinical studies, the cGAS-STING pathway has demonstrated that it is essential for type I IFN production (inflammatory proteins) in tumors, as well as its ability to generate antitumor immune responses.
Autoimmune disease arises when the body’s natural defense system cannot distinguish between its own cells and foreign cells, resulting in the body mistakenly attacking normal cells. There are more than 80 types of autoimmune diseases that affect a wide range of body parts.
Preventing aberrant activation of the cGAS-STING pathway is crucial for maintaining immune homeostasis. If the cGAS-STING pathway is unreasonably activated by lack of regulation, it causes activation of the immune system, resulting in autoimmune diseases.
Several enzymes (RNase H2, TREX1, and DNase II) regulate cGAS activation by controlling the basal level of cytosolic DNA. Mice deficient in these functional enzymes have been shown to develop autoimmune disease with inflammation and lethality in a cGAS- and STING-dependent manner, suggesting a critical role for the cGAS-STING pathway in the pathogenesis of autoimmune diseases.