Predictive biomarkers of response for PD-1/PD-L1 inhibitors: a cumbersome gold rush

Programmed cell death protein 1 (PD-1) and its ligand programmed cell death-ligand 1 (PD-L1) are overexpressed in a number of human malignancies. More interestingly, their expression has been associated with patient survival in non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma, esophageal, pancreatic and colorectal carcinoma, with the data commonly suggesting a negative prognostic role. In this review, we summarize the pros and cons regarding the predictive role of PD-L1 expression in candidate patients for checkpoint inhibitors. Furthermore, we discuss the potential predictive role of other biomarkers, such as tumor mutational burden, microsatellite instability, mismatch repair deficiency and tumor infiltrating lymphocytes. We conclude that PD-L1 testing probably represents simply a “snapshot” of an intricate, fluctuating and dynamic process, that in turn represents the interplay between the immune system and cancer. The PD-L1 assay can be considered more useful for response stratification than in patient selection.