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Immune Checkpoint Inhibitors in the Treatment of Renal Cancer: Current State and Future Perspective

Systemic treatment of renal cancer (RCC) has undergone remarkable changes over the past 20 years with the introduction of immunotherapeutic agents targeting programmed cell death (PD-1)/programmed death-ligand 1 (PD-L1) axis, as a single-agent or combined with anti-CTLA-4 monoclonal antibodies (MoAb...

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Autores principales: Lavacchi, Daniele, Pellegrini, Elisa, Palmieri, Valeria Emma, Doni, Laura, Mela, Marinella Micol, Di Maida, Fabrizio, Amedei, Amedeo, Pillozzi, Serena, Carini, Marco, Antonuzzo, Lorenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369721/
https://www.ncbi.nlm.nih.gov/pubmed/32630154
http://dx.doi.org/10.3390/ijms21134691
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author Lavacchi, Daniele
Pellegrini, Elisa
Palmieri, Valeria Emma
Doni, Laura
Mela, Marinella Micol
Di Maida, Fabrizio
Amedei, Amedeo
Pillozzi, Serena
Carini, Marco
Antonuzzo, Lorenzo
author_facet Lavacchi, Daniele
Pellegrini, Elisa
Palmieri, Valeria Emma
Doni, Laura
Mela, Marinella Micol
Di Maida, Fabrizio
Amedei, Amedeo
Pillozzi, Serena
Carini, Marco
Antonuzzo, Lorenzo
author_sort Lavacchi, Daniele
collection PubMed
description Systemic treatment of renal cancer (RCC) has undergone remarkable changes over the past 20 years with the introduction of immunotherapeutic agents targeting programmed cell death (PD-1)/programmed death-ligand 1 (PD-L1) axis, as a single-agent or combined with anti-CTLA-4 monoclonal antibodies (MoAbs) or a multi-target vascular endothelial growth factor-(VEGF) tyrosine kinase inhibitor (TKI). In this paper, we review the main evidence on the use of Immune Checkpoint Inhibitors (ICIs) for RCC treatment from the first demonstration of activity of a nivolumab single agent in a phase I trial to the novel combination strategies (anti-PD-1 plus anti-CTLA4 or anti-PD-1 plus TKI). In addition, we discuss the use of anti-PD-1/PD-L1 agents in patients with non-clear cells and rare histological subtype RCC. Then, we critically examine the current findings in biomarkers that have been proposed to be prognostic or predictive to the response of immunotherapy including immune gene expression signature, B7-H1 expression, PBRM1 loss of function, PD-L1 expression, frame shift indel count, mutations in bromodomain-containing genes in patients with MiT family translocation RCC (tRCC), high expression of the T-effector gene signature, and a high myeloid inflammation gene expression pattern. To date, a single biomarker as a predictor of response has not been established. Since the dynamic behavior of the immune response and the different impact of ICI treatment on patients with specific RCC subtypes, the integration of multiple biomarkers and further validation in clinical trials are needed.
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spelling pubmed-73697212020-07-21 Immune Checkpoint Inhibitors in the Treatment of Renal Cancer: Current State and Future Perspective Lavacchi, Daniele Pellegrini, Elisa Palmieri, Valeria Emma Doni, Laura Mela, Marinella Micol Di Maida, Fabrizio Amedei, Amedeo Pillozzi, Serena Carini, Marco Antonuzzo, Lorenzo Int J Mol Sci Review Systemic treatment of renal cancer (RCC) has undergone remarkable changes over the past 20 years with the introduction of immunotherapeutic agents targeting programmed cell death (PD-1)/programmed death-ligand 1 (PD-L1) axis, as a single-agent or combined with anti-CTLA-4 monoclonal antibodies (MoAbs) or a multi-target vascular endothelial growth factor-(VEGF) tyrosine kinase inhibitor (TKI). In this paper, we review the main evidence on the use of Immune Checkpoint Inhibitors (ICIs) for RCC treatment from the first demonstration of activity of a nivolumab single agent in a phase I trial to the novel combination strategies (anti-PD-1 plus anti-CTLA4 or anti-PD-1 plus TKI). In addition, we discuss the use of anti-PD-1/PD-L1 agents in patients with non-clear cells and rare histological subtype RCC. Then, we critically examine the current findings in biomarkers that have been proposed to be prognostic or predictive to the response of immunotherapy including immune gene expression signature, B7-H1 expression, PBRM1 loss of function, PD-L1 expression, frame shift indel count, mutations in bromodomain-containing genes in patients with MiT family translocation RCC (tRCC), high expression of the T-effector gene signature, and a high myeloid inflammation gene expression pattern. To date, a single biomarker as a predictor of response has not been established. Since the dynamic behavior of the immune response and the different impact of ICI treatment on patients with specific RCC subtypes, the integration of multiple biomarkers and further validation in clinical trials are needed. MDPI 2020-06-30 /pmc/articles/PMC7369721/ /pubmed/32630154 http://dx.doi.org/10.3390/ijms21134691 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Lavacchi, Daniele
Pellegrini, Elisa
Palmieri, Valeria Emma
Doni, Laura
Mela, Marinella Micol
Di Maida, Fabrizio
Amedei, Amedeo
Pillozzi, Serena
Carini, Marco
Antonuzzo, Lorenzo
Immune Checkpoint Inhibitors in the Treatment of Renal Cancer: Current State and Future Perspective
title Immune Checkpoint Inhibitors in the Treatment of Renal Cancer: Current State and Future Perspective
title_full Immune Checkpoint Inhibitors in the Treatment of Renal Cancer: Current State and Future Perspective
title_fullStr Immune Checkpoint Inhibitors in the Treatment of Renal Cancer: Current State and Future Perspective
title_full_unstemmed Immune Checkpoint Inhibitors in the Treatment of Renal Cancer: Current State and Future Perspective
title_short Immune Checkpoint Inhibitors in the Treatment of Renal Cancer: Current State and Future Perspective
title_sort immune checkpoint inhibitors in the treatment of renal cancer: current state and future perspective
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369721/
https://www.ncbi.nlm.nih.gov/pubmed/32630154
http://dx.doi.org/10.3390/ijms21134691
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