P02.07INTERFERON-β MODULATES THE INNATE IMMUNE RESPONSE AGAINST GLIOBLASTOMA INITIATING CELLS

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2014-09, Vol.16 (Suppl 2), p.ii34-ii34
• Main Authors: Wolpert, F., Happold, C., Roth, P., Reifenberger, G., Weller, M., Eisele, G.
• Format: Article
• Language: English
• Subjects: Poster Presentations
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/nou174.123

The prognosis of glioblastoma remains dismal. Immunotherapy is a promising approach with the need of well-defined targets and potent adjuvants. Glioma-initiating cells (GIC) with stem cell properties are such an attractive target for immunotherapy. However, the immunogenicity of GIC seems limited. Interferon (IFN)-β exerts immune-activating effects like enhanced antigen processing, up-regulation of co-stimulatory molecules and enhanced natural killer (NK) cell activity and thus might enhance an immune response against GIC. Moreover, IFN-β exerts direct anti-GIC cell activities. Thus, IFN-β warrants being further evaluated as an adjuvant for anti-glioblastoma immunotherapies. Here we define the net effect of IFN-β treatment on the innate immunogenicity of GIC. Employing Affymetrix-based transcriptomic profiling, we identified alterations in the expression of several immune regulatory genes in a panel of well-defined GIC lines upon treatment with IFN-β. The up-regulation of immunosuppressive human leukocyte antigen (HLA)-E was contrasted by enhanced surface levels of immune activating nectin-2 while the level of NKG2D ligands remained largely unaltered. In NK cell lysis assays, the immunogenicity of 2 of 3 GIC lines was increased upon IFN-β treatment and further enhanced upon gene silencing of HLA-E using RNA interference. Our data indicate that treatment with IFN-β alters the innate immunogenicity of GIC by increased expression of nectin-2, reverted in part by the concurrent upregulation of HLA-E.