2022
Interferon-γ resistance and immune evasion in glioma develop via Notch-regulated co-evolution of malignant and immune cells
Parmigiani E, Ivanek R, Rolando C, Hafen K, Turchinovich G, Lehmann FM, Gerber A, Brkic S, Frank S, Meyer SC, Wakimoto H, Günel M, Louvi A, Mariani L, Finke D, Holländer G, Hutter G, Tussiwand R, Taylor V, Giachino C. Interferon-γ resistance and immune evasion in glioma develop via Notch-regulated co-evolution of malignant and immune cells. Developmental Cell 2022, 57: 1847-1865.e9. PMID: 35803280, DOI: 10.1016/j.devcel.2022.06.006.Peer-Reviewed Original ResearchConceptsTumor-associated microglia/macrophagesGlioma cellsImmune surveillanceMicroglia/macrophagesImmune cell populationsBrain tumor cellsMouse glioma cellsCytokine expressionImmune attackImmune cellsMouse modelImmune evasionSuppression of NotchTumor cellsNotch inhibitionTumor initiationUpregulation of oncogenesNotch activityCell populationsGliomasCellsSurveillanceLow Notch activityNiche controlTherapy
2017
2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity
Sulkowski PL, Corso CD, Robinson ND, Scanlon SE, Purshouse KR, Bai H, Liu Y, Sundaram RK, Hegan DC, Fons NR, Breuer GA, Song Y, Mishra-Gorur K, De Feyter HM, de Graaf RA, Surovtseva YV, Kachman M, Halene S, Günel M, Glazer PM, Bindra RS. 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. Science Translational Medicine 2017, 9 PMID: 28148839, PMCID: PMC5435119, DOI: 10.1126/scitranslmed.aal2463.Peer-Reviewed Original ResearchConceptsIsocitrate dehydrogenase 1PARP inhibitor sensitivityPossible therapeutic strategiesHomologous recombination defectsTherapeutic strategiesTumor xenograftsInhibitor sensitivityPathologic processesSmall molecule inhibitorsIDH1/2 mutationsTumor progressionIDH2 mutationsMutant IDHPolymerase inhibitorsGlioma cellsTumor cellsHR deficiencyPARP inhibitionIDH mutationsInhibitory effectDehydrogenase 1Neomorphic activityMutant IDH1 enzymeDependent dioxygenasesMutant cells