Recent clinical trials on programmed cell death 1 (PD1)-based immune checkpoint inhibition have confirmed survival benefit in these patients, exploiting the inflammatory immune phenotype, granting Food and Drug Administration approval for the treatment of metastatic mismatch repair–deficient and MSI-high (dMMR-MSI-H) CRC.6, 7, 8, 9 In contrast, mismatch repair–proficient and MSI-low (pMMR-MSI-L) CRC, comprising 85% of the total CRC population, has hardly shown any response to immune checkpoint blockade (ICB).6 This evidence concerns the gene PDCD1 and colorectal carcinoma.