Immunotherapy Progress in Mismatch Repair–Deficient Colorectal Cancer and Future Therapeutic Challenges

Initial investigations of immune-checkpoint therapy targeting Programmed cell death protein 1/programed death ligand 1 in unselected colorectal cancer (CRC) has shown limited to no activity. However, a subset of CRC, characterized by mismatch deficiency or microsatellite instability high (MSI-high), has shown robust early signals of antitumor activity with PD1 targeting. It is now clear that MSI-high CRC represents a unique molecular and immunological tumor subset. Further study and understanding of the immunological microenvironment of these tumors will be critical to continued success with immune-based approaches in MSI-high CRC. This review discusses the current biological understanding of MSI-high CRC and outlines the current and ongoing clinical trials investigating immunotherapy.