title: Interferon-β Modulates the Innate Immune Response against Glioblastoma Initiating Cells.
abstract: Immunotherapy targeting glioblastoma initiating cells (GIC) is considered a promising strategy. However, GIC are prone to evade immune response and there is a need for potent adjuvants. IFN-β might enhance the immune response and here we define its net effect on the innate immunogenicity of GIC. The transcriptomes of GIC treated with IFN-β and controls were assessed by microarray-based expression profiling for altered expression of immune regulatory genes. Several genes involved in adaptive and innate immune responses were regulated by IFN-β. We validated these results using reverse transcription (RT)-PCR and flow cytometry for corresponding protein levels. The up-regulation of the NK cell inhibitory molecules HLA-E and MHC class I was balanced by immune stimulating effects including the up-regulation of nectin-2. In 3 out of 5 GIC lines tested we found a net immune stimulating effect of IFN-β in cytotoxicity assays using NKL cells as effectors. IFN-β therefore warrants further investigation as an adjuvant for immunotherapy targeting GIC.
authors.affiliation: Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, CH-8091, Zurich, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Wolpert
authors.affiliation: Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, CH-8091, Zurich, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Happold
authors.affiliation: Department of Neuropathology, Heinrich Heine University, Moorenstrasse 5, D-40225, Düsseldorf, Germany, and German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
authors.affiliation: Department of Neuropathology, Heinrich Heine University, Moorenstrasse 5, D-40225, Düsseldorf, Germany, and German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Florea
authors.affiliation: Genomics and Transcriptomics Laboratory (GTL), Center for Biological and Medical Research (BMFZ), Heinrich Heine University, Moorenstrasse 5, D-40225, Düsseldorf, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Deenen
authors.affiliation: Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, CH-8091, Zurich, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Roth
authors.affiliation: Department of Neurosurgery, University Hospital Zurich, Frauenklinikstrasse 10, CH-8091, Zurich, Switzerland.
authors.forename: Marian Christoph
authors.initials: MC
authors.lastname: Neidert
authors.affiliation: Department of Neurosurgery, University Hospital Hamburg-Eppendorf, Martinistraße 52, D-20246, Hamburg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Lamszus
authors.affiliation: Department of Neurosurgery, University Hospital Hamburg-Eppendorf, Martinistraße 52, D-20246, Hamburg, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Westphal
authors.affiliation: Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, CH-8091, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.affiliation: Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, CH-8091, Zurich, Switzerland.
authors.forename: Günter
authors.initials: G
authors.lastname: Eisele
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics; D045744:Cell Line, Tumor; D005805:Genes, MHC Class I / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D016899:Interferon-beta / Q000494:pharmacology*; D000075983:Nectins; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; D000075983:Nectins; D016899:Interferon-beta