Fig. 2: Antitumor roles of cGAS.
From: Old dogs, new trick: classic cancer therapies activate cGAS
a Premalignant cells acquire DNA damage during tumorigenesis, subsequently forming micronuclei. DNA in micronuclei are exposed to the cytosol and activate cGAS. cGAS induces cytokines and promotes SASP, which enhances senescence and promotes immune cell-mediated clearance of premalignant cells. b Tumor-derived DNA from dead cancer cells activate cGAS in dendritic cells. Stimulated dendritic cells prime spontaneous antitumor immunity by activating tumor-specific CD8+ T cells and NK cells to kill cancer cells. Similarly, tumor-derived cGAMP from cancer cells is transported to non-cancer cells and activates STING to induce antitumor immunity. c Classic cancer therapies (radiotherapy or chemotherapy) induce DNA damage and micronuclei formation. cGAS in cancer cells is activated by micronuclei to induce the production of type I IFNs and other cytokines; although these cytokines enhance antitumor immunity, they also up-regulate PD-L1 expression on cancer cells.
