Modulation of the CNS innate immune system by the onco-metabolite (R)2-hydroxyglutarate in IDH1 mutant gliomas

The oncometabolite (R)-2-hydroxyglutarate (R-2-HG) produced by isocitrate dehydrogenase 1 (IDH1) mutations plays a role in gliomagenesis via DNA and histone methylation. Existing evidence has shown changes in the immunological composition of IDH1^mut with respect to IDH1^wt GBMs. Here, we plan to generate a detailed spatiotemporal immune cell atlas from IDH1^wt and IDH1^mut gliomas. We further intend to dissect the functional consequences of an abolished Ahr and Tak1 signalling in CNS myeloid cells in IDH1^mut gliomas. In summary, the effects of IDH1 mutations and its oncometabolite R-2-HG on innate immune cells and their pathways involved shall be addressed.