title: HLA-E expression and its clinical relevance in human renal cell carcinoma.
abstract: The non-classical human leukocyte antigen E (HLA-E) expression is frequently overexpressed in tumor diseases, transplants and virus-infected cells and represents an immunomodulatory molecule by binding to the receptors CD94/NKG2A, -B and -C on NK and T cells. Due to its immune suppressive features HLA-E expression might represent an important mechanism of tumors to escape immune surveillance.While an aberrant expression of the non-classical HLA-G antigen in human renal cell carcinoma (RCC) has been demonstrated to be associated with a worse outcome of patients and reduced sensitivity to immune effector cell-mediated cytotoxicity, the expression and function of HLA-E has not yet been analyzed in this tumor entity.Higher levels of HLA-E transcripts were detected in all RCC cell lines and tumor lesions, which were tested in comparison to normal kidney epithelium. Immunohistochemical staining of a tissue microarray (TMA) using the HLA-E-specific monoclonal antibody TFL-033 recognizing the cytoplasmic HLA-E α-chain as monomer revealed a heterogeneous HLA-E expression in RCC lesions with the highest frequency in chromophobe RCC when compared to other RCC subtypes. HLA-E expression did not correlate with the frequency of CD3+, CD4+, CD8+ and FoxP3+ immune cell infiltrations, but showed an inverse correlation with infiltrating CD56+ cells. In contrast to HLA-G, HLA-E expression in RCCs was not statistically significant associated with a decreased disease specific survival. These data suggest that HLA-E overexpression frequently occurs in RCC and correlates with reduced immunogenicity.
authors: Institute of Medical Immunology, Martin-Luther-University, Halle-Wittenberg, Germany.
authors: Barbara
authors: B
authors: Seliger
authors: Institute of Medical Immunology, Martin-Luther-University, Halle-Wittenberg, Germany.
authors: Simon
authors: S
authors: Jasinski-Bergner
authors: Institute of Medical Immunology, Martin-Luther-University, Halle-Wittenberg, Germany.
authors: Dagmar
authors: D
authors: Quandt
authors: Institute of Pathology, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany.
authors: Christine
authors: C
authors: Stoehr
authors: Institute of Medical Immunology, Martin-Luther-University, Halle-Wittenberg, Germany.
authors: Juergen
authors: J
authors: Bukur
authors: Clinics for Urology, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany.
authors: Sven
authors: S
authors: Wach
authors: Clinics for Urology, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany.
authors: Wolfgang
authors: W
authors: Legal
authors: Clinics for Urology, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany.
authors: Helge
authors: H
authors: Taubert
authors: Clinics for Urology, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany.
authors: Bernd
authors: B
authors: Wullich
authors: Institute of Pathology, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany.
authors: Arndt
authors: A
authors: Hartmann
mesh_terms: D002292:Carcinoma, Renal Cell / Q000276:immunology*; D045744:Cell Line, Tumor; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology*; D019139:Tumor Escape / Q000276:immunology*; D000097625:HLA-E Antigens
chemical_list: D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens
keywords: HLA-E; immune escape; non-classical HLA class I; renal cell carcinoma; tumor progression