Isocitrate dehydrogenase mutation and microenvironment in gliomas: Do immunotherapy approaches matter?
Purpose of review - Gliomas with mutations in the gene for isocitrate dehydrogenase (IDH) display a unique immune microenvironment that is distinct from IDH-wildtype gliomas. This unique immune microenvironment is shaped by 2-hydroxyglutarate (2-HG), an oncometabolite produced by mutant I...
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
December 2025
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| In: |
Current opinion in neurology
Year: 2025, Volume: 38, Issue: 6, Pages: 706-710 |
| ISSN: | 1473-6551 |
| DOI: | 10.1097/WCO.0000000000001426 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1097/WCO.0000000000001426 Verlag, lizenzpflichtig, Volltext: https://journals.lww.com/co-neurology/abstract/2025/12000/isocitrate_dehydrogenase_mutation_and.13.aspx 
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| Author Notes: | Michael Platten |
| Summary: | Purpose of review - Gliomas with mutations in the gene for isocitrate dehydrogenase (IDH) display a unique immune microenvironment that is distinct from IDH-wildtype gliomas. This unique immune microenvironment is shaped by 2-hydroxyglutarate (2-HG), an oncometabolite produced by mutant IDH. These features provide an opportunity to develop and test targeted immunotherapies for IDH-mutant gliomas. - Recent findings - IDH-mutant gliomas are characterized by an immunosuppressive tumor immune microenvironment (TIME) that suppresses the infiltration and activation of tumor-specific T cells. This is owed both to direct effects of the oncometabolite 2-hydroxyglutarate on glioma-infiltrating T cells and myeloid cells and indirect effects on the chemotactic profile of tumor cells. These immunosuppressive effects are reversed by IDH inhibitors recently approved for the treatments of IDH-mutant gliomas. At the same time, clinical trials have demonstrated encouraging results for targeted immunotherapies using vaccines targeting the most frequent mutation IDH1R132H. - Summary - The reversal of the immunosuppressive effects by IDH inhibitors has opened exciting avenues for combinatorial immunotherapies such as vaccines and immune checkpoint inhibitors. |
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| Item Description: | Gesehen am 01.12.2025 |
| Physical Description: | Online Resource |
| ISSN: | 1473-6551 |
| DOI: | 10.1097/WCO.0000000000001426 |