cGMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that activates innate 
immune responses. cGAS catalyzes the synthesis of cGAMP, which functions as a 
second messenger that binds and activates the adaptor protein STING to induce 
type I interferons (IFNs) and other immune modulatory molecules. Here we show 
that cGAS is indispensable for the antitumor effect of immune checkpoint 
blockade in mice. Wild-type, but not cGAS-deficient, mice exhibited slower 
growth of B16 melanomas in response to a PD-L1 antibody treatment. Consistently, 
intramuscular delivery of cGAMP inhibited melanoma growth and prolonged the 
survival of the tumor-bearing mice. The combination of cGAMP and PD-L1 antibody 
exerted stronger antitumor effects than did either treatment alone. cGAMP 
treatment activated dendritic cells and enhanced cross-presentation of 
tumor-associated antigens to CD8 T cells. These results indicate that activation 
of the cGAS pathway is important for intrinsic antitumor immunity and that cGAMP 
may be used directly for cancer immunotherapy.