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PD1 and PD-L1 Inhibitors for the Treatment of Kidney Cancer: The Role of PD-L1 Assay

[ Vol. 21 , Issue. 16 ]

Author(s):

Alessia Cimadamore*, Francesco Massari , Matteo Santoni, Antonio Lopez-Beltran , Liang Cheng , Marina Scarpelli, Rodolfo Montironi and Holger Moch   Pages 1664 - 1671 ( 8 )

Abstract:


Background: Immune checkpoint inhibitors targeting the programmed death receptor ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) pathway represent 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 administration of a PD-1 and PDL1 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 a prognostic and predictive biomarker.

Conclusion: So far, 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 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.

Keywords:

Immune-checkpoint inhibitors, immunotherapy, ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, renal cell carcinoma, PD-L1 immunohistochemistry.

Affiliation:

Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Division of Oncology, S. Orsola-Malpighi Hospital, Bologna, Oncology Unit, Macerata Hospital, Macerata, Department of Pathology and Surgery, University of Cordoba, Faculty of Medicine, Cordoba, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Department of Pathology and Molecular Pathology, University and University Hospital Zurich, CH-8091 Zurich



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