Molecular biomarkers allow small populations of patients with relevant molecular defects to have a chance at successful targeted therapy. PD-L1 expression is an emerging biomarker with prognostic implications, as 21-28% of tumors are positive, associated with advanced tumor stage, carcinoma in situ, high grade disease, disease recurrence, cancer-specific survival, overall survival, and lymphocyte invasion. However, there are pitfalls associated with PD-L1 immunohistochemistry expression, namely focal dynamic expression, intra- and inter-tumoral heterogeneity, temporal and spatial evolution remains largely unknown, and the expression is modulated by anti-cancer therapies. Dr. Shariat notes that we also need to be more consistent and standardized in how we perform and report the PD-L1 quantitative expression pattern.
Dr. Shariat concluded his talk by outlining his idea of a “cancer immunogramm” for each patient’s tumor, allowing precise treatment for each individual. Key components of this immunogramm include (i) tumor foreignness (mutational load), (ii) general immune status (lymphocyte count), (iii) immune cell infiltration (intratumoral cells), (iv) absence of checkpoints (PD-L1), absence of soluble inhibitors (IL-6, CRP), absence of inhibitory tumor metabolism (LDH, glucose utilization), and tumor sensitivity to immune effectors (MHC expression and IFN-gamma-sensitivity). Knowledge of these key aspects of every patient’s tumor truly would be a huge step towards personalized medicine. According to Dr. Shariat, precision medicine is the right therapy, for the right tumor, in the right patient, at the right time.
Speaker(s): Shahrokh F. Shariat, Medical University of Vienna, Vienna, Austria
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto
at the #EAU17 - March 24-28, 2017- London, England