HLA-E contributes to an immune-inhibitory phenotype of glioblastoma stem-like cells.

Abstract

Cancer stem cells are an attractive target for immunotherapeutic approaches to glioblastoma. However, an immune inhibitory phenotype of cells currently classified as "glioma-initiating cells" (GIC) might counteract recognition by immune effector cells. Here, we investigate the contribution of the non-classical MHC molecule HLA-E to the immunosuppressive phenotype of GIC. HLA-E is expressed in GIC lines and its expression is reduced upon differentiation of GIC in serum-containing culture conditions. Constitutive HLA-E inhibits natural killer (NK) cell-mediated lysis of GIC since small-interfering RNA-mediated HLA-E gene silencing enhances the immunogenicity of GIC. Increased GIC lysis was observed both in the CD133+ and in the CD133- compartment. Furthermore, the use of interferon-γ as a possible agent to boost an immune response against glioblastoma cells might be limited by the concurrent upregulation of HLA-E.

• Authors: Fabian Wolpert, Patrick Roth, Katrin Lamszus, Ghazaleh Tabatabai, Michael Weller, Günter Eisele
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 250 Issue 1-2 Pg. 27-34 (Sep 15 2012) ISSN: 1872-8421 [Electronic] Netherlands
• PMID: 22688424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Histocompatibility Antigens Class I

Topics

• Brain Neoplasms (immunology)
• Cell Line, Tumor
• Flow Cytometry
• Glioblastoma (immunology)
• Histocompatibility Antigens Class I (immunology)
• Humans
• Killer Cells, Natural (immunology)
• Neoplastic Stem Cells (cytology, immunology)
• Phenotype
• Real-Time Polymerase Chain Reaction
• HLA-E Antigens