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
2020
Targeting glutamine metabolism enhances tumor specific immunity by modulating suppressive myeloid cells
Oh M, Sun I, Zhao L, Leone R, Sun I, Xu W, Collins S, Tam A, Blosser R, Patel C, Englert J, Arwood M, Wen J, Chan-Li Y, Tenora L, Majer P, Rais R, Slusher B, Horton M, Powell J. Targeting glutamine metabolism enhances tumor specific immunity by modulating suppressive myeloid cells. Journal Of Clinical Investigation 2020, 130: 3865-3884. PMID: 32324593, PMCID: PMC7324212, DOI: 10.1172/jci131859.Peer-Reviewed Original ResearchConceptsMyeloid-derived suppressor cellsTumor-associated macrophagesRecruitment of MDSCsGlutamine metabolismMyeloid cellsTumor growthTumor microenvironmentSuppressive myeloid cellsSuppressive immune cellsTumor-specific immunityMyeloid-derived cellsActivation-induced cell deathDevelopment of metastasesImmunogenic cell deathCell deathAntitumor immunityKynurenine levelsSuppressor cellsIDO expressionSpecific immunityImmune cellsTumor glutamine metabolismImmune evasionInflammatory macrophagesSmall molecule inhibitors
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
2017
mTORC2 Signaling Selectively Regulates the Generation and Function of Tissue-Resident Peritoneal Macrophages
Oh M, Collins S, Sun I, Tam A, Patel C, Arwood M, Chan-Li Y, Powell J, Horton M. mTORC2 Signaling Selectively Regulates the Generation and Function of Tissue-Resident Peritoneal Macrophages. Cell Reports 2017, 20: 2439-2454. PMID: 28877476, PMCID: PMC5659290, DOI: 10.1016/j.celrep.2017.08.046.Peer-Reviewed Original ResearchConceptsTissue-resident macrophagesMetabolic reprogrammingTissue-specific cuesUnique differentiation programCritical roleDifferentiation programmingPeritoneal resident macrophagesDifferentiation programMTORC2 activationGATA6 expressionPeritoneal macrophagesResident peritoneal macrophagesTissue microenvironmentHomeostatic functionsReprogrammingSelective roleMacrophage generationMacrophage proliferationDifferentiationDependent fashionResident macrophagesMacrophagesM2 macrophagesGATA6Microenvironment
2016
Asymmetric 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
2007
Airway Exposure Levels of Lipopolysaccharide Determine Type 1 versus Type 2 Experimental Asthma
Kim YK, Oh SY, Jeon SG, Park HW, Lee SY, Chun EY, Bang B, Lee HS, Oh MH, Kim YS, Kim JH, Gho YS, Cho SH, Min KU, Kim YY, Zhu Z. Airway Exposure Levels of Lipopolysaccharide Determine Type 1 versus Type 2 Experimental Asthma. The Journal Of Immunology 2007, 178: 5375-5382. PMID: 17404323, DOI: 10.4049/jimmunol.178.8.5375.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsAsthmaBronchial HyperreactivityFemaleHumansInterferon-gammaInterleukin-12LipopolysaccharidesMaleMiceMice, Inbred BALB CMice, Inbred C57BLMiddle AgedOvalbuminReceptors, Tumor Necrosis FactorRNA, MessengerSignal TransductionSTAT4 Transcription FactorTh1 CellsTh2 CellsTransforming Growth Factor beta1Tumor Necrosis Factor-alphaConceptsHigh-dose LPSLow-dose LPSAsthma phenotypesAdaptive immune responsesImmune responseAirway hyperresponsivenessAllergen sensitizationTNF-alpha receptor-deficient miceType 1IFN-gamma-deficient miceSevere asthma patientsReceptor-deficient miceAllergen-specific IgEExposure levelsIL-12 expressionTNF-alpha expressionIFN-gamma expressionLow LPS levelsNoneosinophilic inflammationAirway inflammationAllergic asthmaNeutrophilic inflammationSevere asthmaAirway exposureAsthma patients