Our experience in lung cancer has enabled us to understand that in spite of the fact that anti-PD-1 agents block the interaction of this receptor with its ligands, PD-L1 and PD-L2, PD-L1’s level of expression does not imply a definitive pattern of response to ICIs in these patients, as several studies propose the use of agents such as Nivolumab, Durvalumab, or Pembrolizumab in perioperative settings in non-small-cell lung cancers (NSCLCs) with a PD-L1 expression lower than 1%, reportedly improving the outcomes of patients [53,54,55]. The gene discussed is PDCD1LG2; the disease is lung cancer.