Interferon-β Modulates the Innate Immune Response against Glioblastoma Initiating Cells

• Published in: PloS one Vol. 10; no. 10; p. e0139603
• Main Authors: Wolpert, Fabian, Happold, Caroline, Reifenberger, Guido, Florea, Ana-Maria, Deenen, René, Roth, Patrick, Neidert, Marian Christoph, Lamszus, Katrin, Westphal, Manfred, Weller, Michael, Eisele, Günter
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.10.2015; Public Library of Science (PLoS)
• Subjects: Adjuvants; Antigens; Brain cancer; Cancer therapies; Cell Adhesion Molecules - genetics; Cell Line, Tumor; Consortia; Cytometry; Cytotoxicity; Dendritic cells; DNA microarrays; Flow cytometry; Gene expression; Gene therapy; Genes; Genes, MHC Class I - genetics; Glioblastoma; Glioblastoma - genetics; Glioblastoma - immunology; Growth factors; Histocompatibility antigen HLA; Histocompatibility Antigens Class I - genetics; Hospitals; Humans; Immune response; Immune system; Immunity, Innate - drug effects; Immunogenicity; Immunotherapy; Innate immunity; Interferon; Interferon-beta - pharmacology; Ligands; Major histocompatibility complex; Medical research; Natural killer cells; Nectin; Nectins; Neurology; Neuropathology; Neurosurgery; Proteins; Reverse transcription; Stem cells; Toxicity; Tumors; Up-Regulation - drug effects; β-Interferon; Switzerland; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0139603

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.