Open AccessNovel landscape of HLA‐G isoforms expressed in clear cell renal cell carcinoma patients
Author(s) -
TronikLe Roux Diana,
Renard Julie,
Vérine Jérôme,
Renault Victor,
Tubacher Emmanuel,
LeMaoult Joel,
RouasFreiss Nathalie,
Deleuze JeanFrançois,
Desgrandschamps François,
Carosella Edgardo D.
Publication year - 2017
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12119
Subject(s) - human leukocyte antigen , cancer research , immune checkpoint , gene isoform , renal cell carcinoma , biology , immunohistochemistry , transmembrane protein , immune system , clear cell renal cell carcinoma , hla g , transcriptome , cancer , antigen , immunotherapy , immunology , pathology , medicine , gene , gene expression , genetics , receptor
Immune checkpoints are powerful inhibitory molecules that promote tumor survival. Their blockade is now recognized as providing effective therapeutic benefit against cancer. Human leukocyte antigen G (HLA‐G), a recently identified immune checkpoint, has been detected in many types of primary tumors and metastases, in malignant effusions as well as on tumor‐infiltrating cells, particularly in patients with clear cell renal cell carcinoma (ccRCC). Here, in order to define a possible anticancer therapy, we used a molecular approach based on an unbiased strategy that combines transcriptome determination and immunohistochemical labeling, to analyze in‐depth the HLA‐G isoforms expressed in these tumors. We found that the expression of HLA‐G is highly variable among tumors and distinct areas of the same tumor, testifying a marked inter‐ and intratumor heterogeneity. Moreover, our results generate an inventory of novel HLA‐G isoforms which includes spliced forms that have an extended 5′‐region and lack the transmembrane and alpha‐1 domains. So far, these isoforms could not be detected by any method available and their assessment may improve the procedure by which tumors are analyzed. Collectively, our approach provides the first extensive portrait of HLA‐G in ccRCC and reveals data that should prove suitable for the tailoring of future clinical applications.