CGAS and neoplasm: Taken together, our findings demonstrate that restricting both endogenous and exogenous serine to CRC cells results in abundant mtDNA-driven, CGAS- and STING-dependent secretion of type I IFN along with restored tumor sensitivity to PD-1 blockage, thereby delineating a novel metabolic mechanism though which malignant cells preserve the mitochondrial immune checkpoint (Figure 1).