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Differences in the frequencies of HLA-class I and II alleles between German patients with renal cell carcinoma and healthy controls

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Abstract

The human leukocyte antigen (HLA) system is a major part of the human immune system and has an impact on tumor initiation, tumor progression, and immunosurveillance. Renal cell carcinoma tumors are considered to be immunogenic. Therefore, we studied the allele frequencies of four gene loci (HLA-A, -B, -C, and HLA-DR) in a cohort of German renal cell carcinoma (RCC) patients and in healthy controls. HLA-A-C were determined using serological methods, whereas HLA-C12, C14, C16, C18, and HLA-DR were characterized through the use of standard molecular biological methods. The occurrence of the HLA-C*12 allele was significantly increased in German RCC patients compared with healthy controls (P < 0.005; Fisher’s exact test), whereas the occurrence of the HLA-DRB1*04 allele was significantly reduced in RCC patients compared with healthy controls (P < 0.05; Fisher’s exact test). However, the presence of allele HLA-C*12 was not significantly associated with 10 year overall survival. We suggest that the frequency of HLA alleles can affect development of RCC and could add knowledge as predictive marker for future immunotherapies.

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Abbreviations

CI:

Confidence interval

HLA:

Human leukocyte antigen

KIRs:

Killer cell immunoglobulin-like receptors

MHC:

Major histocompatibility complex

OS:

Overall survival

PBMCs:

Peripheral blood mononuclear cells

RCC:

Renal cell carcinoma

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Acknowledgements

Helge Taubert was supported by the Dr. Robert Pfleger-Stiftung and by the Rudolf und Irmgard Kleinknecht-Stiftung. We thank American Journal Experts for language editing the manuscript. We are thankful to Dr. Peter Schmidt/Tumorzentrum Martin Luther University Halle-Wittenberg for his help with follow-up data, and Prof. Dr. Hans Heynemann and Dr. Gerit Theil/both Clinic of Urology, Halle for helpful discussions.

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    Authors and Affiliations

    1. Institute of Transfusion Medicine, Martin-Luther-University Halle-Wittenberg, Halle, Germany

      Steffen Goebel

    2. Institute of Medical Microbiology, Martin-Luther-University Halle-Wittenberg, Halle, Germany

      Astrid Kehlen

    3. Institute of Legal Medicine, Martin-Luther-University Halle-Wittenberg, Halle, Germany

      Karen Bluemke

    4. HLA-Laboratory, Martin-Luther-University Halle-Wittenberg, Halle, Germany

      Wolfgang Altermann & Gerald Schlaf

    5. Clinic of Urology, Martin-Luther-University Halle-Wittenberg, Halle, Germany

      Kersten Fischer & Paolo Fornara

    6. Division Molecular Urology, Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Hartmannstr. 14, 91054, Erlangen, Germany

      Bernd Wullich, Sven Wach & Helge Taubert

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    1. Steffen Goebel
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    Correspondence to Helge Taubert.

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    The sponsors, Dr. Robert Pfleger-Stiftung, and Rudolf und Irmgard Kleinknecht-Stiftung had no influence on the study concept, including analysis and interpretation of results.

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    The authors declare that they have no conflict of interest.

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    S. Goebel and A. Kehlen contributed equally.

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    Goebel, S., Kehlen, A., Bluemke, K. et al. Differences in the frequencies of HLA-class I and II alleles between German patients with renal cell carcinoma and healthy controls. Cancer Immunol Immunother 66, 565–571 (2017). https://doi.org/10.1007/s00262-017-1957-3

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    • DOI: https://doi.org/10.1007/s00262-017-1957-3

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