2019
Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion
Leone R, Zhao L, Englert J, Sun I, Oh M, Sun I, Arwood M, Bettencourt I, Patel C, Wen J, Tam A, Blosser R, Prchalova E, Alt J, Rais R, Slusher B, Powell J. Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion. Science 2019, 366: 1013-1021. PMID: 31699883, PMCID: PMC7023461, DOI: 10.1126/science.aav2588.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAzo CompoundsCaproatesCD8-Positive T-LymphocytesCitric Acid CycleEnergy MetabolismFemaleGlucoseGlutamineImmunologic MemoryImmunotherapy, AdoptiveLymphocyte ActivationLymphocytes, Tumor-InfiltratingMaleMice, Inbred BALB CMice, Inbred C57BLNeoplasms, ExperimentalTumor EscapeTumor MicroenvironmentConceptsEffector T cellsT cellsTumor immune evasionCancer cellsPotent antitumor responsesImmune cell functionAntitumor responseImmunosuppressive microenvironmentTumor immunotherapyCancer immunotherapyMice suppressesImmune evasionCell functionOxidative metabolismGlycolytic metabolismGlutamine antagonistImmunotherapyMetabolic characteristicsMetabolic programsTumorsMetabolic checkpointDivergent changesMetabolismCellsAntagonism
2018
mTOR Complex 1 Signaling Regulates the Generation and Function of Central and Effector Foxp3+ Regulatory T Cells
Sun I, Oh M, Zhao L, Patel C, Arwood M, Xu W, Tam A, Blosser R, Wen J, Powell J. mTOR Complex 1 Signaling Regulates the Generation and Function of Central and Effector Foxp3+ Regulatory T Cells. The Journal Of Immunology 2018, 201: 481-492. PMID: 29884702, PMCID: PMC6089237, DOI: 10.4049/jimmunol.1701477.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell DifferentiationFemaleForkhead Transcription FactorsImmunologic MemoryInducible T-Cell Co-Stimulator ProteinLymphocyte ActivationMaleMechanistic Target of Rapamycin Complex 1MiceProgrammed Cell Death 1 ReceptorRegulatory-Associated Protein of mTORSignal TransductionT-Lymphocytes, RegulatoryConceptsT cell activationT cellsCentral TregsGenetic deletionCell activationRegulatory T cell differentiationGeneration of TregsRegulatory T cellsEffector T cellsMemory-like phenotypeT cell differentiationInhibition of mTORSpare respiratory capacityEffector TregsRole of mTORPD-1Treg functionImmune microenvironmentMemory TregsTregsPharmacologic inhibitionDecreased expressionMammalian targetPharmacologic inhibitorsMTOR activity
2015
mTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation
Pollizzi K, Patel C, Sun I, Oh M, Waickman A, Wen J, Delgoffe G, Powell J. mTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation. Journal Of Clinical Investigation 2015, 125: 2090-2108. PMID: 25893604, PMCID: PMC4463194, DOI: 10.1172/jci77746.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCarrier ProteinsCD4-CD8 RatioCD8-Positive T-LymphocytesCell Line, TumorDeoxyglucoseFemaleGenes, ReporterGlycolysisImmunologic MemoryInterferon-gammaLymphocyte ActivationLymphopoiesisMaleMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2Melanoma, ExperimentalMiceMice, CongenicMice, Inbred C57BLMonomeric GTP-Binding ProteinsMultiprotein ComplexesNeuropeptidesOvalbuminPeptide FragmentsPhosphorylationProtein Processing, Post-TranslationalProto-Oncogene Proteins c-aktRapamycin-Insensitive Companion of mTOR ProteinRas Homolog Enriched in Brain ProteinRecombinant Fusion ProteinsSirolimusThymomaTOR Serine-Threonine KinasesTransduction, GeneticTumor Necrosis Factor-alphaConceptsGeneration of CD8T cell effectorsT cellsTuberous sclerosis complex 2Cell effectorsT cell effector responsesMemory-like T cellsEffector cell subsetsT cell memoryDifferentiation of CD4T cell-specific deletionT cell differentiationCell-specific deletionSurface marker expressionMTOR-dependent pathwayEvaluation of miceEffector CD8Antitumor immunityEffector phenotypeEffector cellsCell subsetsRecall responsesVaccine efficacyEffector responsesCD8