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. 2005 Apr;54(4):400-6.
doi: 10.1007/s00262-004-0603-z. Epub 2004 Sep 24.

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

Matthias Wölfl  1 , Achim A Jungbluth, Federico Garrido, Teresa Cabrera, Sharon Meyen-Southard, Rüdiger Spitz, Karen Ernestus, Frank Berthold
Affiliations

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

Matthias Wölfl et al. Cancer Immunol Immunother. 2005 Apr.

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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Figures

Fig. 1
Fig. 1
IHC for CG antigens. a, b Staining with mAb ES121 for NY-ESO-1: a patient no. 11, poorly differentiated neuroblastoma, 250-fold; b patient no. 17, ganglioneuroblastoma, immunoreactivity of mature and immature ganglion cells and no staining of the neuroblasts in the poorly differentiated areas (inlet), 400-fold. c, d Reactivity against mAbM454 for MAGE-A1: c patient no. 11, neuroblasts showing a strong staining intensity (4+), 250-fold; d patient no. 2, focal staining in differentiating neuroblasts, 400-fold. e, f Reactivity against mAb for M3H67 for MAGE-A3/A6: e patient no. 11, 4+, 250-fold; f patient no. 13, 2+, 250-fold.
Fig. 2
Fig. 2
Staining for MHC class I expression in neuroblastoma (patient no. 15). Top staining with mAbW6/32 for HLA-A, HLA-B, HLA-C expression; center mAb GRH1 against β2-m; bottom mAb HC-10 against the MHC heavy chain.
See this image and copyright information in PMC

References

    1. Bernards R, Dessain SK, Weinberg RA. N-myc amplification causes down-modulation of MHC class I antigen expression in neuroblastoma. Cell. 1986;47:667–674. doi: 10.1016/0092-8674(86)90509-X. - DOI - PubMed
    1. Berthold F, Hero B, Kremens B, Handgretinger R, Henze G, Schilling FH, Schrappe M, Simon T, Spix C. Long-term results and risk profiles of patients in five consecutive trials (1979–1997) with stage 4 neuroblastoma over 1 year of age. Cancer Lett. 2003;197:11–17. doi: 10.1016/S0304-3835(03)00076-4. - DOI - PubMed
    1. Cabrera T, Lopez-Nevot MA, Gaforio JJ, Ruiz-Cabello F, Garrido F. Analysis of HLA expression in human tumor tissues. Cancer Immunol Immunother. 2003;52:1–9. - PMC - PubMed
    1. Cheng NC, Beitsma M, Chan A, Op den Camp I, Westerveld A, Pronk J, Versteeg R. Lack of class I HLA expression in neuroblastoma is associated with high N-myc expression and hypomethylation due to loss of the MEMO-1 locus. Oncogene. 1996;13:1737–1744. - PubMed
    1. Christinck ER, Luscher MA, Barber BH, Williams DB. Peptide binding to class I MHC on living cells and quantitation of complexes required for CTL lysis. Nature. 1991;352:67–70. doi: 10.1038/352067a0. - DOI - PubMed

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