P02.07 INTERFERON- beta 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
• ISSN: 1522-8517
• 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)- beta 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- beta exerts direct anti-GIC cell activities. Thus, IFN- beta warrants being further evaluated as an adjuvant for anti-glioblastoma immunotherapies. Here we define the net effect of IFN- beta 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- beta . 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- beta treatment and further enhanced upon gene silencing of HLA-E using RNA interference. Our data indicate that treatment with IFN- beta alters the innate immunogenicity of GIC by increased expression of nectin-2, reverted in part by the concurrent upregulation of HLA-E.