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