Mode of action, new targets and potential biomarkers in modern immunotherapy

Immune checkpoint inhibitors (ICI) have significantly improved the systemic therapy of metastatic disease in genitourinary malignancies. With the European Medicines Agency (EMA) approval of the antibodies nivolumab and pembrolizumab directed against programmed cell death 1 (PD-1) as well as the PD-L1 antibody atezolizumab, three agents are available for the treatment of metastatic urothelial carcinoma and renal cell carcinoma. This article describes the underlying mode of action of PD-1/PD-L1 blockade and other ICIs to activate the immune system for effective tumor rejection. Future therapeutic strategies are focusing on the combination of ICI with targeted therapies to enhance the immune defense, especially in the local tumor microenvironment. Afurther clinical need exists for the establishment of biomarkers to predict atherapy response under ICI, in particular for the role of the PD-L1 status. Biomarkers for predicting primary or acquired therapy resistance are also of clinical importance to enable good patient selection for ICI therapy.