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Erschienen in: Cancer Immunology, Immunotherapy 7/2020

12.03.2020 | Original Article

Comprehensive landscape of immune-checkpoints uncovered in clear cell renal cell carcinoma reveals new and emerging therapeutic targets

verfasst von: Diana Tronik-Le Roux, Mathilde Sautreuil, Mahmoud Bentriou, Jérôme Vérine, Maria Belén Palma, Marina Daouya, Fatiha Bouhidel, Sarah Lemler, Joel LeMaoult, François Desgrandchamps, Paul-Henry Cournède, Edgardo D. Carosella

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 7/2020

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Abstract

Clear cell renal cell carcinoma (ccRCC) constitutes the most common renal cell carcinoma subtype and has long been recognized as an immunogenic cancer. As such, significant attention has been directed toward optimizing immune-checkpoints (IC)-based therapies. Despite proven benefits, a substantial number of patients remain unresponsive to treatment, suggesting that yet unreported, immunosuppressive mechanisms coexist within tumors and their microenvironment. Here, we comprehensively analyzed and ranked forty-four immune-checkpoints expressed in ccRCC on the basis of in‐depth analysis of RNAseq data collected from the TCGA database and advanced statistical methods designed to obtain the group of checkpoints that best discriminates tumor from healthy tissues. Immunohistochemistry and flow cytometry confirmed and enlarged the bioinformatics results. In particular, by using the recursive feature elimination method, we show that HLA-G, B7H3, PDL-1 and ILT2 are the most relevant genes that characterize ccRCC. Notably, ILT2 expression was detected for the first time on tumor cells. The levels of other ligand-receptor pairs such as CD70:CD27; 4-1BB:4-1BBL; CD40:CD40L; CD86:CTLA4; MHC-II:Lag3; CD200:CD200R; CD244:CD48 were also found highly expressed in tumors compared to adjacent non-tumor tissues. Collectively, our approach provides a comprehensible classification of forty-four IC expressed in ccRCC, some of which were never reported before to be co-expressed in ccRCC. In addition, the algorithms used allowed identifying the most relevant group that best discriminates tumor from healthy tissues. The data can potentially assist on the choice of valuable immune-therapy targets which hold potential for the development of more effective anti-tumor treatments.
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Metadaten
Titel
Comprehensive landscape of immune-checkpoints uncovered in clear cell renal cell carcinoma reveals new and emerging therapeutic targets
verfasst von
Diana Tronik-Le Roux
Mathilde Sautreuil
Mahmoud Bentriou
Jérôme Vérine
Maria Belén Palma
Marina Daouya
Fatiha Bouhidel
Sarah Lemler
Joel LeMaoult
François Desgrandchamps
Paul-Henry Cournède
Edgardo D. Carosella
Publikationsdatum
12.03.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 7/2020
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-020-02530-x

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