Alessia Cimadamore*, Francesco Massari , Matteo Santoni, Antonio Lopez-Beltran , Liang Cheng , Marina Scarpelli, Rodolfo Montironi and Holger Moch Pages 1 - 8 ( 8 )
Background: Immune checkpoint inhibitors targeting the programmed death receptor ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) pathway represents a drastic change in the treatment landscape of RCC resulting in a dynamic and evolving scenario. There is an urgent need for predictive biomarkers of response to provide a personalized therapeutic strategy for individual patients.
Objective: In this review we focused on trials that investigated the use of a PD-1 and PD-L1 inhibitor alone or in combination with another agent and compared the different assays applied in each trial to evaluate the role of PD-L1 as prognostic and predictive biomarker.
Conclusion So far, data on the use of PD-L1 expression alone is not sufficient to predict treatment response and present many limitations: the lack of consensus between different methodologies on biomarker assessment, the heterogeneity of PD-L1 between primary tumors and metastatic sites, different criteria of response to therapy (RECIST vs. irRECIST), the complex interplay with inflammatory components, previous treatments, administration of an antibiotic therapy. Combinations of different biomarkers and biological features such as gene expression associated with angiogenesis, immune response and myeloid inflammation are promising biological variables that need to be validated in the context of prospective clinical trials.
immune-checkpoint inhibitors, immunotherapy, ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, renal cell carcinoma, PD-L1 immunohistochemistry
Section of Pathological Anatomy, Polytechnic University of the Marche Region , Division of Oncology, S. Orsola-Malpighi Hospital, Bologna , Oncology Unit, Macerata Hospital , Department of Pathology and Surgery, Faculty of Medicine , Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Section of Pathological Anatomy, Polytechnic University of the Marche Region (Ancona), United Hospitals, Section of Pathological Anatomy, Polytechnic University of the Marche Region (Ancona), United Hospitals , Department of Pathology and Molecular Pathology, University and University Hospital Zurich