2023
Serendipitous Discovery of T Cell–Produced KLK1b22 as a Regulator of Systemic Metabolism
Arwood M, Sun I, Patel C, Sun I, Oh M, Bettencourt I, Claiborne M, Chan-Li Y, Zhao L, Waickman A, Mavrothalassitis O, Wen J, Aja S, Powell J. Serendipitous Discovery of T Cell–Produced KLK1b22 as a Regulator of Systemic Metabolism. ImmunoHorizons 2023, 7: 493-507. PMID: 37358498, PMCID: PMC10580127, DOI: 10.4049/immunohorizons.2300016.Peer-Reviewed Original ResearchConceptsGlucose toleranceT cellsSystemic metabolismGenome ProjectWild-type T cellsMicroarray analysisCell differentiationNovel roleRhebMammalian targetInsulin receptorT cell differentiationReduced glucose toleranceMarked increaseStrains of miceBeige fatExpressionInsulin sensitivityOverexpressionSystemic overexpressionMetabolismCellsMiceToleranceFurther studies
2022
Cutting Edge: mTORC2 Regulates CD8+ Effector and Memory T Cell Differentiation through Serum and Glucocorticoid Kinase 1.
Patel C, Heikamp E, Xu W, Sun I, Oh M, Sun I, Wen J, Tam A, Blosser R, Powell J. Cutting Edge: mTORC2 Regulates CD8+ Effector and Memory T Cell Differentiation through Serum and Glucocorticoid Kinase 1. The Journal Of Immunology 2022, 209: 2287-2291. PMID: 36469844, PMCID: PMC10065985, DOI: 10.4049/jimmunol.2100669.Peer-Reviewed Original ResearchConceptsT cell differentiationT cellsMemory T cell differentiationMemory precursor phenotypeMemory T cellsEfficacy of vaccinesGlucocorticoid-regulated kinase 1Mechanistic targetRapamycin complex 2 (mTORC2) signalingT cell metabolismT cells resultsKinase 1Memory CD8Acute infectionGlucocorticoid kinase 1Tumor immunotherapyCD8Cell differentiationPrecursor phenotypeNuclear translocationPowerful targetSerumRecall capacityEssential regulatorCell metabolism
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 activityInhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT in murine cancer models
Leone R, Sun I, Oh M, Sun I, Wen J, Englert J, Powell J. Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT in murine cancer models. Cancer Immunology, Immunotherapy 2018, 67: 1271-1284. PMID: 29923026, PMCID: PMC11028354, DOI: 10.1007/s00262-018-2186-0.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine A2 Receptor AntagonistsAnimalsAntigens, CDCD8-Positive T-LymphocytesColonic NeoplasmsFemaleGene Expression Regulation, NeoplasticImmunotherapyLymphocyte Activation Gene 3 ProteinLymphocytes, Tumor-InfiltratingMaleMelanoma, ExperimentalMiceMice, Inbred BALB CMice, Inbred C57BLProgrammed Cell Death 1 ReceptorReceptor, Adenosine A2AReceptors, Antigen, T-CellT-Lymphocytes, RegulatoryTumor Cells, CulturedTumor MicroenvironmentXenograft Model Antitumor AssaysConceptsA2AR blockadePD-1T cellsImmune responseA2A receptorsCD39/CD73 axisTumor immune evasionEffector T cellsLAG-3 expressionRegulatory T cellsT cell persistenceTumor bearing miceAdenosine A2A receptorsMurine cancer modelsCoinhibitory receptorsCheckpoint blockadeCheckpoint therapyRegulatory cellsLymph nodesImmunologic responseImmunotherapy regimensInflammatory milieuPharmacologic blockadeA2AR antagonistAdenosine levels
2016
Deletion of mTORC1 Activity in CD4+ T Cells Is Associated with Lung Fibrosis and Increased γδ T Cells
Vigeland C, Collins S, Chan-Li Y, Hughes A, Oh M, Powell J, Horton M. Deletion of mTORC1 Activity in CD4+ T Cells Is Associated with Lung Fibrosis and Increased γδ T Cells. PLOS ONE 2016, 11: e0163288. PMID: 27649073, PMCID: PMC5029914, DOI: 10.1371/journal.pone.0163288.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBleomycinCD4-Positive T-LymphocytesDisease Models, AnimalInterleukin-17MacrophagesMechanistic Target of Rapamycin Complex 1MiceMice, KnockoutMultiprotein ComplexesNeutrophilsPulmonary FibrosisReceptors, Antigen, T-Cell, gamma-deltaSignal TransductionT-Lymphocyte SubsetsTOR Serine-Threonine KinasesConceptsΓδ T cellsTh17 cellsDevelopment of fibrosisT cellsPulmonary fibrosisIL-17AChronic inflammationCytokines IL-17ADevelopment of bleomycinNovel therapeutic targetLung dysfunctionLung neutrophilsProgressive fibrosisLung fibrosisM2 macrophagesTherapeutic targetFibrosisIncurable diseaseInflammationMortalityBleomycinCellsILCritical rolePrior studiesAsymmetric inheritance of mTORC1 kinase activity during division dictates CD8+ T cell differentiation
Pollizzi K, Sun I, Patel C, Lo Y, Oh M, Waickman A, Tam A, Blosser R, Wen J, Delgoffe G, Powell J. Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8+ T cell differentiation. Nature Immunology 2016, 17: 704-711. PMID: 27064374, PMCID: PMC4873361, DOI: 10.1038/ni.3438.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell DifferentiationCell DivisionCell SurvivalCells, CulturedFemaleGlycolysisImmunologic MemoryLipid MetabolismLysosomesMaleMechanistic Target of Rapamycin Complex 1MiceMice, Inbred C57BLMice, TransgenicMultiprotein ComplexesPrecursor Cells, T-LymphoidProtein TransportReceptors, Antigen, T-CellSignal TransductionTOR Serine-Threonine Kinases
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