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

PLoS One. 2015 Oct 6;10(10):e0139603. doi: 10.1371/journal.pone.0139603. eCollection 2015.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion Molecules / genetics
  • Cell Line, Tumor
  • Genes, MHC Class I / genetics
  • Glioblastoma / genetics
  • Glioblastoma / immunology*
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Immunity, Innate / drug effects*
  • Interferon-beta / pharmacology*
  • Nectins
  • Up-Regulation / drug effects


  • Cell Adhesion Molecules
  • Histocompatibility Antigens Class I
  • Nectins
  • Interferon-beta

Grants and funding

This work was supported by the Swiss National Science Foundation (SNF 31003A_130122 to M. Weller), The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.