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

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

PLoS One. 2015;10(10):e0139603

Authors: Wolpert F, Happold C, Reifenberger G, Florea AM, Deenen R, Roth P, Neidert MC, Lamszus K, Westphal M, Weller M, Eisele G

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.

PMID: 26441059 [PubMed - in process]