Immunotherapy in Renal Cell Carcinoma: Latest Evidence and Clinical Implications

Overview

Journal Drugs Context

Specialty Pharmacology

Date 2018 Jun 15

PMID 29899754

Citations 41

Authors

Matteo Santoni

Francesco Massari

Vincenzo Di Nunno

Alessandro Conti

Alessia Cimadamore

Marina Scarpelli

Rodolfo Montironi

Liang Cheng

Nicola Battelli

Antonio Lopez-Beltran

Affiliations

Soon will be listed here.

Abstract

Advances in understanding the mechanisms of tumour-induced immunosuppression have led to the development of immune-checkpoint inhibitors in cancer patients, including those with renal cell carcinoma (RCC). The optimal combination between immunotherapy and targeted agents (as well as the possible favourable sequential therapy of these two classes of drugs) remains an open question at this moment. Several trials are currently underway to assess the combination of anti-programmed-death 1 (PD-1) or anti-PD-ligand(L)1 agents with other immunotherapies or with anti-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). In this editorial, we described the results of the most recent clinical trials on the use of immunotherapies in RCC and the emerging data on the research for reliable biomarkers of tumour response in this setting. In addition, we have focused on the role of the gut microbiome and tumour microenvironment in the development of future therapeutic strategies for RCC patients.

Citing Articles

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SETD2 Loss and ATR Inhibition Synergize to Promote cGAS Signaling and Immunotherapy Response in Renal Cell Carcinoma.

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References

Montironi R, Santoni M, Cheng L, Lopez-Beltran A, Massari F, Matrana M . An Overview of Emerging Immunotargets of Genitourinary Tumors. Curr Drug Targets. 2015; 17(7):750-6. DOI: 10.2174/1389450117666151209144649. View

Piva F, Giulietti M, Occhipinti G, Santoni M, Massari F, Sotte V . Computational analysis of the mutations in BAP1, PBRM1 and SETD2 genes reveals the impaired molecular processes in renal cell carcinoma. Oncotarget. 2015; 6(31):32161-8. PMC: 4741666. DOI: 10.18632/oncotarget.5147. View

Santoni M, Santini D, Massari F, Conti A, Iacovelli R, Burattini L . Heterogeneous drug target expression as possible basis for different clinical and radiological response to the treatment of primary and metastatic renal cell carcinoma: suggestions from bench to bedside. Cancer Metastasis Rev. 2013; 33(1):321-31. DOI: 10.1007/s10555-013-9453-5. View

Motzer R, Hutson T, Glen H, Michaelson M, Molina A, Eisen T . Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015; 16(15):1473-1482. DOI: 10.1016/S1470-2045(15)00290-9. View

Hipp M, Hilf N, Walter S, Werth D, Brauer K, Radsak M . Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses. Blood. 2008; 111(12):5610-20. DOI: 10.1182/blood-2007-02-075945. View

Powles T, Chowdhury S, Bower M, Saunders N, Lim L, Shamash J . The effect of sunitinib on immune subsets in metastatic clear cell renal cancer. Urol Int. 2010; 86(1):53-9. DOI: 10.1159/000319498. View

Hutson T, Escudier B, Esteban E, Bjarnason G, Lim H, Pittman K . Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2013; 32(8):760-7. PMC: 5569683. DOI: 10.1200/JCO.2013.50.3961. View

Choueiri T, Escudier B, Powles T, Mainwaring P, Rini B, Donskov F . Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015; 373(19):1814-23. PMC: 5024539. DOI: 10.1056/NEJMoa1510016. View

Motzer R, Hutson T, Tomczak P, Michaelson M, Bukowski R, Rixe O . Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007; 356(2):115-24. DOI: 10.1056/NEJMoa065044. View

10.

Massari F, Santoni M, Ciccarese C, Santini D . The immunocheckpoints in modern oncology: the next 15 years. Expert Opin Biol Ther. 2015; 15(7):917-21. DOI: 10.1517/14712598.2015.1035251. View

11.

Routy B, Le Chatelier E, Derosa L, Duong C, Alou M, Daillere R . Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2017; 359(6371):91-97. DOI: 10.1126/science.aan3706. View

12.

Montironi R, Santoni M, Tartari F, Lopez-Beltran A, Cheng L, Berardi R . Testing PD-1/PD-L1 Expression in Cancer Therapy: Pathologic Insights and Economic Sustainability. Arch Pathol Lab Med. 2016; 140(6):501-2. DOI: 10.5858/arpa.2015-0529-LE. View

13.

Kucharczyk J, Matrana M, Santoni M, Massari F, Scarpelli M, Cheng L . Emerging Immunotargets in Metastatic Renal Cell Carcinoma. Curr Drug Targets. 2015; 17(7):771-6. DOI: 10.2174/1389450117666151209115753. View

14.

Santoni M, Rizzo M, Burattini L, Farfariello V, Berardi R, Santoni G . Present and future of tyrosine kinase inhibitors in renal cell carcinoma: analysis of hematologic toxicity. Recent Pat Antiinfect Drug Discov. 2012; 7(2):104-10. DOI: 10.2174/157489112801619719. View

15.

Motzer R, Tannir N, Mcdermott D, Frontera O, Melichar B, Choueiri T . Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018; 378(14):1277-1290. PMC: 5972549. DOI: 10.1056/NEJMoa1712126. View

16.

Iacovelli R, Nole F, Verri E, Renne G, Paglino C, Santoni M . Prognostic Role of PD-L1 Expression in Renal Cell Carcinoma. A Systematic Review and Meta-Analysis. Target Oncol. 2015; 11(2):143-8. DOI: 10.1007/s11523-015-0392-7. View

17.

Ciccarese C, Alfieri S, Santoni M, Santini D, Brunelli M, Bergamini C . New toxicity profile for novel immunotherapy agents: focus on immune-checkpoint inhibitors. Expert Opin Drug Metab Toxicol. 2015; 12(1):57-75. DOI: 10.1517/17425255.2016.1120287. View

18.

Santoni M, De Giorgi U, Iacovelli R, Conti A, Burattini L, Rossi L . Pre-treatment neutrophil-to-lymphocyte ratio may be associated with the outcome in patients treated with everolimus for metastatic renal cell carcinoma. Br J Cancer. 2013; 109(7):1755-9. PMC: 3790174. DOI: 10.1038/bjc.2013.522. View

19.

Santoni M, Massari F, Amantini C, Nabissi M, Maines F, Burattini L . Emerging role of tumor-associated macrophages as therapeutic targets in patients with metastatic renal cell carcinoma. Cancer Immunol Immunother. 2013; 62(12):1757-68. PMC: 11029754. DOI: 10.1007/s00262-013-1487-6. View

20.

Motzer R, Escudier B, Oudard S, Hutson T, Porta C, Bracarda S . Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors. Cancer. 2010; 116(18):4256-65. DOI: 10.1002/cncr.25219. View