While there is solid clinical evidence for the therapeutic role of immune checkpoint inhibitors in mismatch repair-deficient (dMMR) and in highly microsatellite instable (MSI-H) metastatic CRC (mCRC), blockade of CTLA-4 or PD-L1/PD-1 as monotherapy has not conferred any major clinical benefit to patients with MMR-proficient (pMMR) or microsatellite stable (MSS) mCRC, reflecting 95% of the CRC population. This evidence concerns the gene CTLA4 and colorectal carcinoma.