[The Potential of a Novel Therapeutic Strategy for Colorectal Cancer Targeting the cGAS-STING Pathway].

The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)pathway is one of the important intracellular signaling pathways responsible for the recognition of exogenous DNA and subsequent induction of type Ⅰ interferon responses. Interestingly, in recent years, the importance of the cGAS-STING pathway in promoting anti-tumor immune responses has been highlighted. Decreased expression of cGAS-STING in tumor cells was reported in various cancers, including colorectal cancer(CRC), and it has been found to be involved in inhibiting the anti-tumor immune responses. In our recent investigation, we specifically examined the impact of tumor cell-intrinsic cGAS-STING pathway on the activation of immune cells within the CRC tumor microenvironment, focusing on mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H)and mismatch repair proficient/microsatellite stable(pMMR/MSS)CRCs. We revealed that cGAS-STING expression in tumor cells was decreased in pMMR/MSS CRC compared to dMMR/MSI-H CRC, which correlated with the decreased infiltration of cytotoxic T cells. Here, we discuss the possibility of a novel therapeutic strategy for CRC targeting the tumor cell-intrinsic cGAS-STING pathway based on the findings from recent studies.