IDH2 and central nervous system cancer: IDH-mutant astrocytomas and oligodendrogliomas (IDH-As and IDH-Os) share the same developmental hierarchy and lineage of glial differentiation, and the volume differences between them can be largely explained by discrete TME and landmark genetic events, as tumor grade increased, malignant cell proliferation was enhanced, undifferentiated glioma cells increased, and macrophage expression programs overtook microglia in the TME (4).