While the introduction of immunotherapy with Programmed Death 1, Programmed Death-Ligand 1 (PD-1 or PD-L1) or Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) immune checkpoint inhibitors (ICIs) has deeply changed the treatment algorithm of different tumour types [7–11], the benefit from ICIs is restricted to the small subset of mCRC patients, approximately 3–5% of cases, with microsatellite instability-high (MSI-high) or deficient mismatch repair (dMMR) tumours. This evidence concerns the gene CD274 and neoplasm.