Interferon-? 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-? 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-? 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-?. 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-? in cytotoxicity assays using NKL cells as effectors. IFN-? therefore warrants further investigation as an adjuvant for immunotherapy targeting GIC.

SUBMITTER: Wolpert F 

PROVIDER: S-EPMC4595134 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature