2024
Targeting STAT3 in tumor-associated antigen-presenting cells as a strategy for kidney and bladder cancer immunotherapy
Alcantara M, Tang W, Wang D, Kaniowski D, Kang E, Dizman N, Chehrazi-Raffle A, Meza L, Zengin Z, Hall J, Hsu J, Egelston C, Moreira D, Horsager A, Pal S, Kortylewski M. Targeting STAT3 in tumor-associated antigen-presenting cells as a strategy for kidney and bladder cancer immunotherapy. Frontiers In Immunology 2024, 14: 1274781. PMID: 38259453, PMCID: PMC10800835, DOI: 10.3389/fimmu.2023.1274781.Peer-Reviewed Original ResearchImmune checkpoint blockadeDendritic cellsCancer patientsBladder cancerT cellsTumor-associated antigen-presenting cellsTherapeutic efficacyLesser extent IL-10T cell-based immunotherapyImmune checkpoint inhibitorsTumor immune evasionAntitumor immune responseCD8 T cellsRegulatory T cellsBladder cancer immunotherapyCell-based immunotherapyAntigen-presenting cellsSTAT3 activationRenal cancer patientsBladder cancer patientsImmune cell activityMyeloid immune cellsICB resistanceIpilimumab immunotherapyCheckpoint inhibitors
2022
DENR controls JAK2 translation to induce PD-L1 expression for tumor immune evasion
Chen B, Hu J, Hu X, Chen H, Bao R, Zhou Y, Ye Y, Zhan M, Cai W, Li H, Li HB. DENR controls JAK2 translation to induce PD-L1 expression for tumor immune evasion. Nature Communications 2022, 13: 2059. PMID: 35440133, PMCID: PMC9018773, DOI: 10.1038/s41467-022-29754-y.Peer-Reviewed Original ResearchConceptsPD-L1 expressionTumor immune evasionImmune evasionReduced PD-L1 expressionDeath ligand 1Tumor-killing activityT cellsTherapeutic targetTumor growthCancer cellsCRISPR/Cas9 screeningLigand 1Cell homeostasisKinase 2ExpressionEvasionCD8ImmunotherapyCellsIFNγDysfunctionRBP dysfunctionTumorsCancerPI3K activation allows immune evasion by promoting an inhibitory myeloid tumor microenvironment
Collins NB, Al Abosy R, Miller BC, Bi K, Zhao Q, Quigley M, Ishizuka JJ, Yates KB, Pope HW, Manguso RT, Shrestha Y, Wadsworth M, Hughes T, Shalek AK, Boehm JS, Hahn WC, Doench JG, Haining WN. PI3K activation allows immune evasion by promoting an inhibitory myeloid tumor microenvironment. Journal For ImmunoTherapy Of Cancer 2022, 10: e003402. PMID: 35264433, PMCID: PMC8915320, DOI: 10.1136/jitc-2021-003402.Peer-Reviewed Original ResearchConceptsImmune evasionCheckpoint blockadePI3K activationMouse syngeneic tumor modelsPharmacological PI3K inhibitionEfficacy of immunotherapyNumber of CD8Tumor immune evasionTumor immune microenvironmentRational combination strategiesSyngeneic tumor modelsCell-extrinsic effectsK activationPI3K inhibitionMyeloid microenvironmentImmune microenvironmentPoor responseMyeloid infiltrationT cellsImmune responseImmunotherapyMyeloid cellsImmune systemPhospho-inositol-3 kinaseTumor microenvironment
2021
KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements
Zhang SM, Cai WL, Liu X, Thakral D, Luo J, Chan LH, McGeary MK, Song E, Blenman KRM, Micevic G, Jessel S, Zhang Y, Yin M, Booth CJ, Jilaveanu LB, Damsky W, Sznol M, Kluger HM, Iwasaki A, Bosenberg MW, Yan Q. KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements. Nature 2021, 598: 682-687. PMID: 34671158, PMCID: PMC8555464, DOI: 10.1038/s41586-021-03994-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorDNA-Binding ProteinsEpigenesis, GeneticGene SilencingHeterochromatinHistone-Lysine N-MethyltransferaseHumansInterferon Type IJumonji Domain-Containing Histone DemethylasesMaleMelanomaMiceMice, Inbred C57BLMice, KnockoutNuclear ProteinsRepressor ProteinsRetroelementsTumor EscapeConceptsImmune checkpoint blockadeImmune evasionCheckpoint blockadeImmune responseAnti-tumor immune responseRobust adaptive immune responseTumor immune evasionAnti-tumor immunityAdaptive immune responsesType I interferon responseDNA-sensing pathwayMouse melanoma modelImmunotherapy resistanceMost patientsCurrent immunotherapiesTumor immunogenicityImmune memoryMelanoma modelCytosolic RNA sensingRole of KDM5BConsiderable efficacyInterferon responseImmunotherapyEpigenetic therapyBlockadeKIR3DL3 Is an Inhibitory Receptor for HHLA2 that Mediates an Alternative Immunoinhibitory Pathway to PD1
Bhatt R, Berjis A, Konge J, Mahoney K, Klee A, Freeman S, Chen C, Jegede O, Catalano P, Pignon J, Sticco-Ivins M, Zhu B, Hua P, Soden J, Zhu J, McDermott D, Arulanandam A, Signoretti S, Freeman G. KIR3DL3 Is an Inhibitory Receptor for HHLA2 that Mediates an Alternative Immunoinhibitory Pathway to PD1. Cancer Immunology Research 2021, 9: 156-169. PMID: 33229411, PMCID: PMC8284010, DOI: 10.1158/2326-6066.cir-20-0315.Peer-Reviewed Original ResearchConceptsClear cell renal cell carcinomaTumor immune evasionImmune evasionInhibitory receptorsT cellsKiller cell immunoglobulin-like receptorsImmune inhibitory pathwaysCell renal cell carcinomaNatural killer cellsImmunoglobulin-like receptorsRenal cell carcinomaImmune inhibitory activityImmunoinhibitory pathwayImmunoregulatory ligandsRelated SpotlightPDL1 expressionKiller cellsPD1 pathwayHHLA2 expressionCell carcinomaB7 familyCostimulatory effectCostimulatory signalsEffective cancer therapyHHLA2
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
2013
Clinical and pharmacodynamic (PD) results of a phase I trial with AMP-224 (B7-DC Fc) that binds to the PD-1 receptor.
Infante J, Powderly J, Burris H, Kittaneh M, Grice J, Smothers J, Brett S, Fleming M, May R, Marshall S, Devenport M, Pillemer S, Pardoll D, Chen L, Langermann S, LoRusso P. Clinical and pharmacodynamic (PD) results of a phase I trial with AMP-224 (B7-DC Fc) that binds to the PD-1 receptor. Journal Of Clinical Oncology 2013, 31: 3044-3044. DOI: 10.1200/jco.2013.31.15_suppl.3044.Peer-Reviewed Original ResearchPD-1B7-H1T cellsFunctional T cell responsesT cell effector functionPK/PD relationshipInflammatory adverse eventsPD-1 axisAdvanced solid tumorsPre-treatment biopsiesTumor immune evasionPhase I trialT cell poolT cell responsesInitial disease progressionPD-1 receptorCell effector functionsFunctional T cellsMultiple tumor typesBaseline tumorPD-1highStable diseaseB7-DCLymphocyte subsetsAdverse events
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