André and colleagues present the final report on the impactful results of the Keynote-177 trial after 5 years of OS follow-up.1 The roots of this breakthrough that has led to the incorporation of anti-PD-1 agents into the treatment algorithm of patients with MSI-H/MMRD tumors stretch back to 1993, when Manuel Perucho and Bert Vogelstein respective teams described the molecular features that defined this unique subset of colorectal cancers with a distinctive genotype and clinical phenotype.2-6 While Perucho’s team reported the accumulations of clustered mutations in microsatellite DNA regions, Vogelstein’s team was able to find the existence of mutations in mismatch repair (MMR) genes.