How mutant isocitrate dehydrogenase orchestrates immune cells
Astrocytomas and oligodendrogliomas, World Health Organization grades 2-4, are signified by recurrent mutations in the genes for mutant isocitrate dehydrogenase (IDH) types 1 and 2. The neomorphic enzymatic activity of mutant IDH causes epigenetic reprogramming by histone and DNA hypermethylation vi...
Gespeichert in:
| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2022
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| In: |
Neuro-Oncology
Year: 2022, Jahrgang: 24, Heft: 2, Pages: 210-212 |
| ISSN: | 1523-5866 |
| DOI: | 10.1093/neuonc/noab266 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/neuonc/noab266
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| Verfasserangaben: | Lukas Bunse and Michael Platten |
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| 520 | |a Astrocytomas and oligodendrogliomas, World Health Organization grades 2-4, are signified by recurrent mutations in the genes for mutant isocitrate dehydrogenase (IDH) types 1 and 2. The neomorphic enzymatic activity of mutant IDH causes epigenetic reprogramming by histone and DNA hypermethylation via the excessive production of the oncometabolite R-2-hydroxyglutarate (R-2-HG), ultimately driving dedifferentiation and malignant transformation. Therefore, small molecule mutant IDH inhibitors have been developed to re-differentiate glioma cells in early-stage gliomas.In recent years, a plethora of data has been collected highlighting mutant IDH as a key suppressor of spontaneous and therapy-induced anti-glioma immunity. On the one hand, mutant IDH excludes T cells from the glioma microenvironment (GME) by inhibition of glioma cell signal transducer and activator of transcription 1 (STAT1) transcriptional activity followed by reduced C-X-C motif chemokine ligand 10 (CXCL10)-dependent recruitment of cytotoxic T cells. On the other, its neomorphic enzymatic product R-2-HG incapacitates yet infiltrating T cells by paracrine inhibition of calcium-dependent T cell receptor signaling and polyamine biosynthesis and induces apoptosis of intratumoral T cells.1-3 | ||
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