In response to the challenges of low sensitivity and resistance faced by IDH mutation inhibitors, Wu and colleagues have engineered mouse models with IDH1 mutations and uncovered that tumor maintenance is mediated by dual (R)-2-hydroxyglutarate activities: suppression of CD8+ T cell activity and the autonomous inactivation of TET2 DNA demethylase within tumor cells (Wu et al., 2022a). This evidence concerns the gene IDH2 and neoplasm.