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

干扰素-β 调节针对胶质母细胞瘤起始细胞的先天免疫反应

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作者:Fabian Wolpert, Caroline Happold, Guido Reifenberger, Ana-Maria Florea, René Deenen, Patrick Roth, Marian Christoph Neidert, Katrin Lamszus, Manfred Westphal, Michael Weller, Günter Eisele

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.

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