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WHO grade associated downregulation of MHC class I antigen-processing machinery components in human astrocytomas: does it reflect a potential immune escape mechanism?

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Abstract

Defects of major histocompatibility complex (MHC) class I antigen-processing machinery (APM) components have been shown to contribute to immune escape of malignant cells. We investigated the expression of APM components in astrocytomas without detectable defects in HLA class I antigen expression and correlated it with grade of malignancy. Quantitative immunohistochemical analysis of astrocytomas revealed reduced expression of the cytosolic proteasome subunit low molecular weight protein 2 (LMP2), the endoplasmatic reticulum (ER) transporter associated with antigen processing-1 (TAP1), and the ER chaperone β2-microglobulin (β2m) in astrocytoma cells when compared to astrocytes from nonpathological brain. Among human WHO grade II–IV astrocytomas, downregulation of LMP2, TAP1 and β2m correlated with grade of malignancy. Furthermore, astrocytoma cell lines (n = 12) expressed all APM components analyzed at levels comparable to dendritic cells (DC), which were used for comparative purposes. However, upregulation of β2m after stimulation with inflammatory cytokines was significantly lower in astrocytoma cell lines than in control cells. Our results support the hypothesis that coordinated downregulation or impaired upregulation of certain HLA class I APM components may serve as a mechanism for astrocytoma cells to evade the host’s immune response, even if HLA class I antigen surface expression is not altered.

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Authors and Affiliations

  1. Department of General Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany

    Matthias Mehling, Michael Weller & Heinz Wiendl

  2. Outpatient Clinic Neurology, University Hospitals of Basel, Petersgraben 4, 4031, Basel, Switzerland

    Matthias Mehling

  3. Institute of Brain Research, University of Tübingen, Calwer Str. 3, 72076, Tübingen, Germany

    Perikles Simon, Michel Mittelbronn & Richard Meyermann

  4. Department V, Sports Medicine/ Internal Medicine, University of Tübingen, Silcherstr. 5, 72076, Tübingen, Germany

    Perikles Simon

  5. Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York, 14263, USA

    Soldano Ferrone

  6. Department of Neurology, University of Würzburg, Josef-Schneider-Strasse 11, 97080, Würzburg, Germany

    Heinz Wiendl

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  1. Matthias Mehling
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Correspondence to Heinz Wiendl.

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Mehling, M., Simon, P., Mittelbronn, M. et al. WHO grade associated downregulation of MHC class I antigen-processing machinery components in human astrocytomas: does it reflect a potential immune escape mechanism?. Acta Neuropathol 114, 111–119 (2007). https://doi.org/10.1007/s00401-007-0231-8

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  • DOI: https://doi.org/10.1007/s00401-007-0231-8

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