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