Immunotherapy for colorectal cancer: insight from inherited genetics

Immunotherapy shows efficacy for multiple cancer types and potential for expanded use. However, current immune checkpoint inhibitors (ICIs) are ineffective against microsatellite-stable colorectal cancer (CRC), which is more commonly diagnosed. Immunotherapy strategies for non-responsive CRC, including new targets and new combination therapies, are being tested to address this need. Importantly, a subset of inherited germline genetic variants associated with CRC risk are predicted to regulate genes with immune functions, including genes related to existing ICIs, as well as new potential targets in the major histocompatibility complex (MHC) region and immunoregulatory cytokines. We review discoveries in the inherited genetics of CRC related to the immune system and draw connections with ongoing developments and emerging immunotherapy targets.