PD-1 and PD-L1 as immunotherapy targets and biomarkers in non-small cell lung cancer

The integration of immunotherapeutic agents in the treatment of non-small cell lung cancer (NSCLC) has revolutionized the approach of the prevalent type of lung cancer. Although PD-1 and its ligands (PD-L1 and PD-L2) are stimulating molecules of the immune-checkpoint pathway, with primary function to limit inflammatory response and autoimmunity, tumor cells have found a way to exploit these molecules by obtaining the opportunity to respond with PD-L1 expression in cytokine signals and thus to evade immune surveillance. Several immunotherapeutic agents targeting these molecules have already been tested and show quick and remarkable responses and survival prolongation in about 14-20% of chemo-resistant patients in NSCLC, resulting to FDA approval of some PD-1 inhibitors (pebrolizumab, nivolumab), even for first-line treatment of patients with metastatic NSCLC whose tumors have high PD-L1 expression (pebrolizumab). Regarding to the prognostic value of PD-L1 and PD-1 expression as biomarkers in NSCLC, the results still remain contradictory. However, the elevated expression of PD-L1 has been correlated with higher efficacy of the various immunotherapeutic agents, implying a high predictive value of this biomarker, even if the truth about specificity and sensitivity of the aforementioned molecules is generally more complicated.