Independent association of PD-L1 expression with noninactivated VHL clear cell renal cell carcinoma-A finding with therapeutic potential.

Details

Serval ID
serval:BIB_9B7C88D6D513
Type
Article: article from journal or magazin.
Collection
Publications
Title
Independent association of PD-L1 expression with noninactivated VHL clear cell renal cell carcinoma-A finding with therapeutic potential.
Journal
International journal of cancer
Author(s)
Kammerer-Jacquet S.F., Crouzet L., Brunot A., Dagher J., Pladys A., Edeline J., Laguerre B., Peyronnet B., Mathieu R., Verhoest G., Patard J.J., Lespagnol A., Mosser J., Denis M., Messai Y., Gad-Lapiteau S., Chouaib S., Belaud-Rotureau M.A., Bensalah K., Rioux-Leclercq N.
ISSN
1097-0215 (Electronic)
ISSN-L
0020-7136
Publication state
Published
Issued date
01/01/2017
Peer-reviewed
Oui
Volume
140
Number
1
Pages
142-148
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor that is characterized in most cases by inactivation of the tumor suppressor gene VHL. The VHL/HIF/VEGF pathway thus plays a major role in angiogenesis and is currently targeted by anti-angiogenic therapy. The emergence of resistance is leading to the use of targeted immunotherapy against immune checkpoint PD1/PDL1 that restores antitumor immune response. The correlation between VHL status and PD-L1 expression has been little investigated. In this study, we retrospectively reviewed 98 consecutive cases of ccRCC and correlated PD-L1 expression by immunohistochemistry (IHC) with clinical data (up to 10-year follow-up), pathological criteria, VEGF, PAR-3, CAIX and PD-1 expressions by IHC and complete VHL status (deletion, mutation and promoter hypermethylation). PD-L1 expression was observed in 69 ccRCC (70.4%) and the corresponding patients had a worse prognosis, with a median specific survival of 52 months (p = 0.03). PD-L1 expression was significantly associated with poor prognostic factors such as a higher ISUP nucleolar grade (p = 0.01), metastases at diagnosis (p = 0.01), a sarcomatoid component (p = 0.04), overexpression of VEGF (p = 0.006), and cytoplasmic PAR-3 expression (p = 0.01). PD-L1 expression was also associated with dense PD-1 expression (p = 0.007) and with ccRCC with 0 or 1 alteration(s) (non-inactivated VHL tumors; p = 0.007) that remained significant after multivariate analysis (p = 0.004 and p = 0.024, respectively). Interestingly, all wild-type VHL tumors (no VHL gene alteration, 11.2%) expressed PD-L1. In this study, we found PD-L1 expression to be associated with noninactivated VHL tumors and in particular wild-type VHL ccRCC, which may benefit from therapies inhibiting PD-L1/PD-1.
Keywords
Adult, Aged, Aged, 80 and over, B7-H1 Antigen/metabolism, Carcinoma, Renal Cell/genetics, Carcinoma, Renal Cell/metabolism, Carcinoma, Renal Cell/pathology, Female, Gene Expression Regulation, Neoplastic, Humans, Lung Neoplasms/genetics, Lung Neoplasms/metabolism, Lung Neoplasms/pathology, Male, Middle Aged, Multivariate Analysis, Prognosis, Retrospective Studies, Survival Analysis, Von Hippel-Lindau Tumor Suppressor Protein/genetics, PD-L1 expression, VHL status, clear cell renal cell carcinoma, clinical outcome
Pubmed
Web of science
Create date
28/06/2022 8:26
Last modification date
11/11/2023 8:10
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