Codo, Paula and Weller, Michael and Meister, Gunter and Szabo, Emese and Steinle, Alexander and Wolter, Marietta and Reifenberger, Guido and Roth, Patrick (2014) MicroRNA-mediated down-regulation of NKG2D ligands contributes to glioma immune escape. ONCOTARGET, 5 (17). pp. 7651-7662. ISSN 1949-2553,
Full text not available from this repository. (Request a copy)Abstract
Malignant gliomas are intrinsic brain tumors with a dismal prognosis. They are well-adapted to hypoxic conditions and poorly immunogenic. NKG2D is one of the major activating receptors of natural killer (NK) cells and binds to several ligands (NKG2DL). Here we evaluated the impact of miRNA on the expression of NKG2DL in glioma cells including stem-like glioma cells. Three of the candidate miRNA predicted to target NKG2DL were expressed in various glioma cell lines as well as in glioblastomas in vivo: miR-20a, miR-93 and miR-106b. LNA inhibitor-mediated miRNA silencing up-regulated cell surface NKG2DL expression, which translated into increased susceptibility to NK cell-mediated lysis. This effect was reversed by neutralizing NKG2D antibodies, confirming that enhanced lysis upon miRNA silencing was mediated through the NKG2D system. Hypoxia, a hallmark of glioblastomas in vivo, down-regulated the expression of NKG2DL on glioma cells, associated with reduced susceptibility to NK cell-mediated lysis. This process, however, was not mediated through any of the examined miRNA. Accordingly, both hypoxia and the expression of miRNA targeting NKG2DL may contribute to the immune evasion of glioma cells at the level of the NKG2D recognition pathway. Targeting miRNA may therefore represent a novel approach to increase the immunogenicity of glioblastoma.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NEWLY-DIAGNOSED GLIOBLASTOMA; MALIGNANT GLIOMA; RECEPTOR NKG2D; NK CELLS; ACTIVATING RECEPTOR; TGF-BETA; EXPRESSION; BEVACIZUMAB; RESPONSES; THERAPY; glioma; immune escape; NKG2D; miRNA |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Aug 2019 12:54 |
| Last Modified: | 13 Aug 2019 12:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9543 |
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