CTLA4 and colorectal carcinoma: Therefore, while immune checkpoint inhibitors—such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 agents—have demonstrated efficacy as frontline therapy as reported in the KEYNOTE-177 study in patients with previously-treated dMMR CRC who have progressed on fluoropyrimidines, oxaliplatin, and irinotecan [6], they fail to provide benefit to 95% of patients with mCRC defined as proficient mismatch repair (pMMR) or microsatellite stable (MSS) tumors.