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- W2743001310 abstract "Abstract Background Diffuse gliomas are fatal primary brain tumors that are poorly immunogenic. The basis for insufficient anti-tumor immunity in diffuse gliomas is not understood. Mutations in isocitrate dehydrogenases (IDH1 and IDH2) promote diffuse glioma formation through epigenetic reprogramming of a number of genes, including immune-related genes. Here, we identify epigenetic dysregulation of natural killer (NK) cell ligand genes as significant contributors to immune escape in glioma. Methods We analyzed the TCGA database for immune gene expression patterns in IDH mutant or wild-type gliomas and identified differentially expressed immune genes. NKG2D ligands expression levels and NK cell-mediated lysis were measured in patient-derived glioma stem cells and in genetically engineered astrocytes. Finally, we assessed the impact of hypomethylating agent Decitabine as a potential NK cell sensitizing agent in IDH mutant cells. Results All IDH mutant glioma stem-like cell lines exhibited significantly lower expression of NKG2D ligands compared with IDH wild-type cells. Consistent with these findings, IDH mutant glioma cells and astrocytes were resistant to NK cell-mediated lysis. The hypomethylating agent Decitabine increased NKG2D ligand expression, and restored NK- mediated lysis of IDH mutant cells in an NKG2D-dependent manner. Conclusions IDH mutant glioma cells acquire resistance to NK cells through epigenetic silencing of NKG2D ligands ULBP1 and ULPB3. Decitabine-mediated hypomethylation restores ULBP1 and ULBP3 expression in IDH mutant glioma cells and may provide a clinically useful method to sensitize IDH mutant gliomas to NK cell-mediated immune surveillance in patients with IDH mutated diffuse gliomas." @default.
- W2743001310 created "2017-08-17" @default.
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- W2743001310 date "2016-05-01" @default.
- W2743001310 modified "2023-09-28" @default.
- W2743001310 title "IDH Mutant Gliomas Escape Natural Killer Cell Immune Surveillance by Downregulation of NKG2D Ligand Expression" @default.
- W2743001310 doi "https://doi.org/10.4049/jimmunol.196.supp.142.11" @default.
- W2743001310 hasPublicationYear "2016" @default.
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