It binds with high affinity to its receptor, blocking the PD-1 interaction with its ligands (PD-L1 and PD-L2) on tumor cells, thereby rejuvenating T-cell activity and fostering anti-tumor immune responses.329 Nivolumab was approved by the FDA in 2014 for advanced melanoma and subsequently for additional malignancies such as NSCLC, renal cell carcinoma, and Hodgkin’s lymphoma, and CRC.330 Ongoing and completed clinical studies have explored nivolumab both as a standalone treatment and in combination with other therapeutic agents for CRC, especially in advanced or metastatic settings. This evidence concerns the gene PDCD1 and colorectal carcinoma.