HLA-E expression and its clinical relevance in human renal cell carcinoma
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Barbara Seliger1, Simon Jasinski-Bergner1, Dagmar Quandt1, Christine Stoehr2, Juergen Bukur1, Sven Wach3, Wolfgang Legal3, Helge Taubert3, Bernd Wullich3, Arndt Hartmann2
1Institute of Medical Immunology, Martin-Luther-University, Halle-Wittenberg, Germany
2Institute of Pathology, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany
3Clinics for Urology, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany
Barbara Seliger, email: Barbara.Seliger@uk-halle.de
Keywords: HLA-E, non-classical HLA class I, renal cell carcinoma, tumor progression, immune escape
Received: April 11, 2016 Accepted: July 27, 2016 Published: August 31, 2016
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.
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