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Volume 21
Issue 13
10.3390/ijms21134691
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Review

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

by
Daniele Lavacchi
1,
Elisa Pellegrini
1,
Valeria Emma Palmieri
1,
Laura Doni
1,
Marinella Micol Mela
1,
Fabrizio Di Maida
1,
Amedeo Amedei
2,
Serena Pillozzi
1,
Marco Carini
1,2 and
Lorenzo Antonuzzo
1,2,*
1
Clinical Oncology Unit, AOU Careggi, 50134 Firenze, Italy
2
Department of Experimental and Clinical Medicine, University of Firenze, 50134 Firenze, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(13), 4691; https://doi.org/10.3390/ijms21134691
Submission received: 26 May 2020 / Revised: 18 June 2020 / Accepted: 25 June 2020 / Published: 30 June 2020
(This article belongs to the Section Molecular Immunology)
Review Reports Versions Notes

Abstract

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.
Keywords: immune checkpoint inhibitors; renal cell carcinoma; tyrosine kinase inhibitors; predictive biomarkers immune checkpoint inhibitors; renal cell carcinoma; tyrosine kinase inhibitors; predictive biomarkers

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MDPI and ACS Style

Lavacchi, D.; Pellegrini, E.; Palmieri, V.E.; Doni, L.; Mela, M.M.; Di Maida, F.; Amedei, A.; Pillozzi, S.; Carini, M.; Antonuzzo, L. Immune Checkpoint Inhibitors in the Treatment of Renal Cancer: Current State and Future Perspective. Int. J. Mol. Sci. 2020, 21, 4691. https://doi.org/10.3390/ijms21134691

AMA Style

Lavacchi D, Pellegrini E, Palmieri VE, Doni L, Mela MM, Di Maida F, Amedei A, Pillozzi S, Carini M, Antonuzzo L. Immune Checkpoint Inhibitors in the Treatment of Renal Cancer: Current State and Future Perspective. International Journal of Molecular Sciences. 2020; 21(13):4691. https://doi.org/10.3390/ijms21134691

Chicago/Turabian Style

Lavacchi, Daniele, Elisa Pellegrini, Valeria Emma Palmieri, Laura Doni, Marinella Micol Mela, Fabrizio Di Maida, Amedeo Amedei, Serena Pillozzi, Marco Carini, and Lorenzo Antonuzzo. 2020. "Immune Checkpoint Inhibitors in the Treatment of Renal Cancer: Current State and Future Perspective" International Journal of Molecular Sciences 21, no. 13: 4691. https://doi.org/10.3390/ijms21134691

APA Style

Lavacchi, D., Pellegrini, E., Palmieri, V. E., Doni, L., Mela, M. M., Di Maida, F., Amedei, A., Pillozzi, S., Carini, M., & Antonuzzo, L. (2020). Immune Checkpoint Inhibitors in the Treatment of Renal Cancer: Current State and Future Perspective. International Journal of Molecular Sciences, 21(13), 4691. https://doi.org/10.3390/ijms21134691

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