Atlantis exploration: predictive biomarkers to immunotherapy response

The emergence and continuous development of immune checkpoint inhibitors (ICIs) therapy brings a revolution in cancer therapy history including urothelial carcinoma. Early accurate targeting and adequate treatment are critical to patient prognosis and overall survival. To overcome these limitations, two strategies are actively being pursued: identification of predictive biomarkers for clinical response to ICIs and multi-pronged combination therapies. Biomarkers might allow clinicians to practice a precision medicine approach in ICIs (biomarker-based patient selection). The development of predictive biomarkers is needed to optimize patient benefit, minimize risk of toxicities, and guide combination approaches. The greatest focus in clinical trials and reviews has been on tumor-cell PD-L1 expression. Although PD-L1 positivity enriches for populations with clinical benefit, PD-L1 testing alone is insufficient for patient selection in most malignancies. In this review, we discuss the status of PD-L1 testing and explore emerging data on new biomarker strategies with tumor-infiltrating lymphocytes, mutational burden, immune gene signatures, microsatellite instability and molecular subtypes.