HLA-E contributes to an immune-inhibitory phenotype of glioblastoma stem-like cells.
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.
Department of Neurology, University Hospital Zürich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland.
Fabian
F
Wolpert
Patrick
P
Roth
Katrin
K
Lamszus
Ghazaleh
G
Tabatabai
Michael
M
Weller
Günter
G
Eisele
D001932:Brain Neoplasms / Q000276:immunology*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005909:Glioblastoma / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000276:immunology*; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D000097625:HLA-E Antigens
D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens