biostudies-literatureChuntova PNCI NIH HHSNINDS NIH HHSe004644https://www.ebi.ac.uk/biostudies/studies/S-EPMC9174833biostudies-literatureUnknown10(5)<h4>Background</h4>Long-term prognosis of WHO grade II, isocitrate dehydrogenase (IDH)-mutated low-grade glioma (LGG) is poor due to high risks of recurrence and malignant transformation into high-grade glioma. Immunotherapy strategies are attractive given the relatively intact immune system of patients with LGG and the slow tumor growth rate. However, accumulation of the oncometabolite D-2-hydroxyglutarate (D-2HG) in IDH-mutated gliomas leads to suppression of inflammatory pathways in the tumor microenvironment, thereby contributing to the 'cold' tumor phenotype. Inhibiting D-2HG production presents an opportunity to generate a robust antitumor response following tumor antigen vaccination and immune checkpoint blockade.<h4>Methods</h4>An IDH1^R132H glioma model was created in syJournal for immunotherapy of cancerInhibition of D-2HG leads to upregulation of a proinflammatory gene signature in a novel HLA-A2/HLA-DR1 transgenic mouse model of IDH1R132H-expressing glioma.PMC9174833R01 CA222965R35 NS105068T32 CA151022Mende ALOkada HHudson CTron AENarayanaswamy RNejo TYamamichi ADiebold DMontoya MLu MRonseaux SChuntova PNicolay BDowney KMChen THyer MLfalseInhibition of D-2HG leads to upregulation of a proinflammatory gene signature in a novel HLA-A2/HLA-DR1 transgenic mouse model of IDH1R132H-expressing glioma.<h4>Background</h4>Long-term prognosis of WHO grade II, isocitrate dehydrogenase (IDH)-mutated low-grade glioma (LGG) is poor due to high risks of recurrence and malignant transformation into high-grade glioma. Immunotherapy strategies are attractive given the relatively intact immune system of patients with LGG and the slow tumor growth rate. However, accumulation of the oncometabolite D-2-hydroxyglutarate (D-2HG) in IDH-mutated gliomas leads to suppression of inflammatory pathways in the tumor microenvironment, thereby contributing to the 'cold' tumor phenotype. Inhibiting D-2HG production presents an opportunity to generate a robust antitumor response following tumor antigen vaccination and immune checkpoint blockade.<h4>Methods</h4>An IDH1^R132H glioma model was created in sy2022-01-01T00:00:00Z2022 May2026-06-15T06:00:56.56Z2025-04-05T23:17:13.715ZS-EPMC91748333560608710.1136/jitc-2022-004644