Although a recent trial, KEYNOTE-177 [99], has established the antitumor efficacy of ICIs in treatment-naïve advanced CRC, only patients harboring deficient-MMR/MS-instable tumors are eligible for using ICIs, with the rationale being that a high mutational burden from deficient-MMR/MS-instability results in overexpression of immunogenic antigens and upregulation of immune checkpoint proteins [100]. This evidence concerns the gene MRC1 and colorectal carcinoma.