Title:PD1 and PD-L1 Inhibitors for the Treatment of Kidney Cancer: The Role of PD-L1 Assay
Volume: 21
Issue: 16
Author(s): Alessia Cimadamore*, Francesco Massari , Matteo Santoni, Antonio Lopez-Beltran , Liang Cheng , Marina Scarpelli, Rodolfo Montironi and Holger Moch
Affiliation:
- Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona,Italy
Keywords:
Immune-checkpoint inhibitors, immunotherapy, ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab,
renal cell carcinoma, PD-L1 immunohistochemistry.
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.