Immune Checkpoint Inhibition in Metastatic Colorectal Cancer Harboring Microsatellite Instability or Mismatch Repair Deficiency

Simple Summary Microsatellite instability (MSI) is a molecular indicator of defective DNA mismatch repair (dMMR). MSI/dMMR status is observed in approximately 5% of metastatic colorectal cancers (mCRC) but 10–18% of localized colorectal cancers. MSI/dMMR status is a major predictive biomarker for the efficacy of immune checkpoint inhibitors (ICIs). This review presents the current and future challenges of ICIs for patients with MSI/dMMR colorectal cancer. Abstract Microsatellite instability (MSI) is a tumor phenotype related to a deficient DNA mismatch repair system (dMMR). This phenotype, observed in 5% of metastatic mCRC but 10–18% of localized CRC, is associated with high tumor mutational burden with highly immunogenic neoantigens. It has emerged as a major predictive biomarker for the efficacy of ICIs. In this review, we will present a comprehensive overview of the literature concerning the efficacy of ICIs in MSI/dMMR mCRC, with a focus on new developments in first-line metastatic setting. Then, we will present current and future challenges of immuno-oncology for patients with MSI/dMMR metastatic CRC.