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
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
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
2012
Epicutaneous Exposure to Staphylococcal Superantigen Enterotoxin B Enhances Allergic Lung Inflammation via an IL-17A Dependent Mechanism
Yu J, Oh MH, Park JU, Myers AC, Dong C, Zhu Z, Zheng T. Epicutaneous Exposure to Staphylococcal Superantigen Enterotoxin B Enhances Allergic Lung Inflammation via an IL-17A Dependent Mechanism. PLOS ONE 2012, 7: e39032. PMID: 22848348, PMCID: PMC3407176, DOI: 10.1371/journal.pone.0039032.Peer-Reviewed Original ResearchConceptsIL-17A-dependent mechanismsAtopic dermatitisAirway hyperresponsivenessAtopic marchLung inflammationDependent mechanismDevelopment of ADSeverity of ADEnterotoxin BSystemic Th2 responseAllergic lung inflammationTh17/ILSkin barrier abnormalitiesIL-6 productionSkin of patientsEpicutaneous exposureAllergic rhinitisIL-17ATh2 responsesEpicutaneous sensitizationLymph nodesImmune environmentLesional skinAllergen ovalbuminStimulating lymphocytes
2007
TH2 and TH1 lung inflammation induced by airway allergen sensitization with low and high doses of double-stranded RNA
Jeon SG, Oh SY, Park HK, Kim YS, Shim EJ, Lee HS, Oh MH, Bang B, Chun EY, Kim SH, Gho YS, Zhu Z, Kim YY, Kim YK. TH2 and TH1 lung inflammation induced by airway allergen sensitization with low and high doses of double-stranded RNA. Journal Of Allergy And Clinical Immunology 2007, 120: 803-812. PMID: 17610940, DOI: 10.1016/j.jaci.2007.05.030.Peer-Reviewed Original ResearchConceptsRespiratory viral infectionsAllergen sensitizationLung inflammationViral infectionAirway sensitizationIL-4Immune responseMouse modelHigh dosesIL-13-deficient miceIFN-gamma-deficient miceT-bet-deficient miceToll-like receptor 3Airway allergen exposureAllergic lung inflammationAdaptive immune responsesToll-like receptorsIL-4 expressionSTAT6-deficient miceNovel mouse modelIFN-gamma expressionAllergen exposurePathophysiologic mechanismsIL-13Deficient miceAirway 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