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Expression of MHC class I, MHC class II, and cancer germline antigens in neuroblastoma

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Abstract

Background: Neuroblastoma is the most common solid extracranial tumor in childhood, still with poor survival rates for metastatic disease. Neuroblastoma cells are of neuroectodermal origin and express a number of cancer germline (CG) antigens. These CG antigens may represent a potential target for immunotherapy such as peptide-based vaccination strategies. Objective: The purpose of this study was to analyze the presence of MAGE-A1, MAGE-A3/A6, and NY-ESO-1 on an mRNA and protein level and to determine the expression of MHC class I and MHC class II antigens within the same tumor specimens. Methods: A total of 68 tumors were available for RT-PCR, and 19/68 tumors were available for immunohistochemical (IHC) analysis of MAGE-A1, MAGE-A3/A6, and NY-ESO-1. In parallel, the same tumors were stained with a panel of antibodies for MHC class I and MHC class II molecules. Results: Screening of 68 tumor specimens by RT-PCR revealed expression of MAGE-A1 in 44%, MAGE-A3/A6 in 21%, and NY-ESO-1 in 28% of cases. Immunohistochemistry for CG antigens of selected tumors showed good agreement between protein and gene expression. However, staining revealed a heterogeneous expression of CG antigens. None of the selected tumors showed MHC class I or MHC class II expression. Conclusions: mRNA expression of MAGE-A1, MAGE-A3/A6, and NY-ESO-1 is congruent with the protein expression as determined by immunohistochemistry. The heterogeneous CG-antigen expression and the lack of MHC class I and II molecules may have implications for T-cell–mediated immunotherapy in neuroblastoma.

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Acknowledgements

We thank Ulla Schlütter for excellent technical assistance. This work was supported in part by the Kinderkrebs-Neuroblastomforschung e.V, Germany.

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Authors and Affiliations

  1. Children’s Hospital, Department of Pediatric Hematology and Oncology, University of Cologne, Cologne, Germany

    Matthias Wölfl, Sharon Meyen-Southard, Rüdiger Spitz, Karen Ernestus & Frank Berthold

  2. Ludwig Institute for Cancer Research at Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Achim A. Jungbluth

  3. Departamento de Analisis Clinicos, Hospital Universitario Virgen des las Nieves, Granada, Spain

    Federico Garrido & Teresa Cabrera

  4. Program in Immunology, Fred Hutchinson Cancer Research Center, D3-100, 1100 Fairview Avenue N, PO Box 19024, Seattle, WA, 98109, USA

    Matthias Wölfl

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  1. Matthias Wölfl
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Correspondence to Matthias Wölfl.

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Wölfl, M., Jungbluth, A.A., Garrido, F. et al. Expression of MHC class I, MHC class II, and cancer germline antigens in neuroblastoma. Cancer Immunol Immunother 54, 400–406 (2005). https://doi.org/10.1007/s00262-004-0603-z

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