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

Project Summary

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 IDH1mut with respect to IDH1wt GBMs. Here, we plan to generate a detailed spatiotemporal immune cell atlas from IDH1wt and IDH1mut gliomas. We further intend to dissect the functional consequences of an abolished Ahr and Tak1 signalling in CNS myeloid cells in IDH1mut 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.