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
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
2014
The AGC kinase SGK1 regulates TH1 and TH2 differentiation downstream of the mTORC2 complex
Heikamp E, Patel C, Collins S, Waickman A, Oh M, Sun I, Illei P, Sharma A, Naray-Fejes-Toth A, Fejes-Toth G, Misra-Sen J, Horton M, Powell J. The AGC kinase SGK1 regulates TH1 and TH2 differentiation downstream of the mTORC2 complex. Nature Immunology 2014, 15: 457-464. PMID: 24705297, PMCID: PMC4267697, DOI: 10.1038/ni.2867.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsAsthmaCell DifferentiationCells, CulturedEndosomal Sorting Complexes Required for TransportGene Expression RegulationHepatocyte Nuclear Factor 1-alphaImmediate-Early ProteinsInterferon-gammaMechanistic Target of Rapamycin Complex 2Melanoma, ExperimentalMiceMice, Inbred C57BLMice, KnockoutMultiprotein ComplexesNedd4 Ubiquitin Protein LigasesPoxviridae InfectionsProtein Serine-Threonine KinasesT Cell Transcription Factor 1Th1 CellsTh2 CellsTOR Serine-Threonine KinasesTranscription FactorsTumor BurdenUbiquitin-Protein LigasesVaccinia virus