Immunotherapy-related biomarkers: Confirmations and uncertainties

Immunotherapy profoundly changed oncology treatment, becoming one of the main therapeutical strategies. Remarkable improvement has been achieved in survival outcomes, but the percentage of patients who benefit from immunotherapy is still limited. Only one-third of patients receiving immune checkpoint inhibitors (ICIs) achieve long-term response. Several patients are not responsive to treatment or relapse after an initial response. To date, programmed death-ligand 1, microsatellite instability, and tumor mutational burden are the three biomarkers validated to predict the ICIs response, but a single variable seems still insufficient in the patient's selection. Considering the substantial and increasing use of these drugs, the identification of new predictive biomarkers of ICI response is of paramount importance. We summarize the state of the art and the clinical use of immune biomarkers in oncology, highlighting the strength and weaknesses of currently approved biomarkers, describing the emerging tissues and circulating biomarkers, and outlining future perspectives.