Current markers and their value in the era of immuno-oncology

Immunotherapy in urothelial cancer is a quickly evolving field as new agents are being investigated in multiple clinical trials and various clinical settings. The purpose of this review is to provide an insight into the mechanism of these treatments, potential targets to evaluate treatment response and to give an update on the current status of clinical trials. Urothelial cancer is a polyclonal disease with a substantial tumor heterogeneity and a high mutational load which may be beneficial as this may trigger a stronger T-cell mediated immune response. PD-1 expression has been shown to correlate with stage, grade, progression and poorer survival but it appears challenging to be utilized as a predictor for treatment response in urothelial cancer. Another important concept is immune cell (IC) infiltration, which is a reflection of the activated immune response within the target tissue. Marker genes may represent signaling pathways involved in T-cell recognition and lysis of T-cells. The complexity of the tumor and host interaction requires multiple concepts to be integrated into a future model to assess treatment response. We have evaluated multiple biomarker approaches currently investigated in clinical trials in urothelial cancer.