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Acta Neuropathologica

, Volume 114, Issue 2, pp 111–119 | Cite as

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

  • Matthias Mehling
  • Perikles Simon
  • Michel Mittelbronn
  • Richard Meyermann
  • Soldano Ferrone
  • Michael Weller
  • Heinz Wiendl
Original Paper

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.

Keywords

MHC Antigen-processing machinery Astrocytoma Immune escape 

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Matthias Mehling
    • 1
    • 2
  • Perikles Simon
    • 3
    • 4
  • Michel Mittelbronn
    • 3
  • Richard Meyermann
    • 3
  • Soldano Ferrone
    • 5
  • Michael Weller
    • 1
  • Heinz Wiendl
    • 1
    • 6
  1. 1.Department of General NeurologyHertie-Institute for Clinical Brain Research, University of TübingenTübingenGermany
  2. 2.Outpatient Clinic NeurologyUniversity Hospitals of BaselBaselSwitzerland
  3. 3.Institute of Brain ResearchUniversity of TübingenTübingenGermany
  4. 4.Department V, Sports Medicine/ Internal MedicineUniversity of TübingenTübingenGermany
  5. 5.Department of ImmunologyRoswell Park Cancer InstituteBuffaloUSA
  6. 6.Department of NeurologyUniversity of WürzburgWürzburgGermany

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