2019
B cell depletion or absence does not impede anti-tumor activity of PD-1 inhibitors
Damsky W, Jilaveanu L, Turner N, Perry C, Zito C, Tomayko M, Leventhal J, Herold K, Meffre E, Bosenberg M, Kluger HM. B cell depletion or absence does not impede anti-tumor activity of PD-1 inhibitors. Journal For ImmunoTherapy Of Cancer 2019, 7: 153. PMID: 31200747, PMCID: PMC6567557, DOI: 10.1186/s40425-019-0613-1.Peer-Reviewed Original ResearchConceptsPD-1 inhibitorsB cell contentB-cell depletionAnti-tumor activityB cellsMuMT miceCell depletionAnti-PD-1 inhibitorsAnti-PD-1 responseB-cell depleting drugsTumor-infiltrating B cellsImpaired B-cell functionT cell-dependent tumor rejectionPD-1 inhibitionMC38 colon cancerB cell functionAnti-tumor effectsB-cell malignanciesMurine cancer modelsCell contentOverall survivalTumor rejectionCD20 antibodyAutoimmune disordersTumor shrinkage
2018
Myeloid-targeted immunotherapies act in synergy to induce inflammation and antitumor immunity
Perry CJ, Muñoz-Rojas AR, Meeth KM, Kellman LN, Amezquita RA, Thakral D, Du VY, Wang JX, Damsky W, Kuhlmann AL, Sher JW, Bosenberg M, Miller-Jensen K, Kaech SM. Myeloid-targeted immunotherapies act in synergy to induce inflammation and antitumor immunity. Journal Of Experimental Medicine 2018, 215: 877-893. PMID: 29436395, PMCID: PMC5839759, DOI: 10.1084/jem.20171435.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD40 AntigensCell ProliferationImmunotherapyInflammationInterferon-gammaMacrophagesMelanoma, ExperimentalMiceMyeloid CellsNeoplasmsPhenotypeProto-Oncogene Proteins B-rafPTEN PhosphohydrolaseReceptors, Granulocyte-Macrophage Colony-Stimulating FactorRNA, MessengerSurvival AnalysisT-LymphocytesTranscription, GeneticTumor Necrosis Factor-alphaConceptsCombination therapyEffective antitumor immune responseProtective T cell responsesTumor-associated myeloid cellsM2-like stateCheckpoint inhibitor therapyAntitumor immune responseT cell responsesCSF-1R inhibitorAntitumor immunityInhibitor therapySuch patientsIL-12IL-6Cancer immunotherapyTAM subsetsUntreated tumorsT cellsImmune responseMouse modelTherapeutic targetTAM subpopulationsMyeloid cellsTumor growthCell responses
2017
IL-7 plays a critical role for the homeostasis of allergen-specific memory CD4 T cells in the lung and airways
Yeon SM, Halim L, Chandele A, Perry CJ, Kim SH, Kim SU, Byun Y, Yuk SH, Kaech SM, Jung YW. IL-7 plays a critical role for the homeostasis of allergen-specific memory CD4 T cells in the lung and airways. Scientific Reports 2017, 7: 11155. PMID: 28894184, PMCID: PMC5593957, DOI: 10.1038/s41598-017-11492-7.Peer-Reviewed Original ResearchConceptsMediastinal lymph nodesCD4 T cellsMemory T cellsT cellsAllergen-specific memory T cellsMemory CD4 T cellsMemory Th2 cellsIL-7 signalingAirway inflammationAllergen exposureAntigen exposureLymph nodesAllergic diseasesHomeostatic proliferationAllergic patientsRecall responsesTh2 cellsIL-7Murine modelAirwayViral infectionLungDependent fashionHomeostatic turnoverCells
2015
Prostaglandin E2 and programmed cell death 1 signaling coordinately impair CTL function and survival during chronic viral infection
Chen JH, Perry CJ, Tsui YC, Staron MM, Parish IA, Dominguez CX, Rosenberg DW, Kaech SM. Prostaglandin E2 and programmed cell death 1 signaling coordinately impair CTL function and survival during chronic viral infection. Nature Medicine 2015, 21: 327-334. PMID: 25799228, PMCID: PMC4505619, DOI: 10.1038/nm.3831.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsBcl-2-Like Protein 11CelecoxibCell SurvivalDinoprostoneFemaleLymphocytic ChoriomeningitisLymphocytic choriomeningitis virusMembrane ProteinsMiceMice, Inbred C57BLMice, TransgenicProgrammed Cell Death 1 ReceptorProto-Oncogene ProteinsPyrazolesReceptors, Prostaglandin E, EP2 SubtypeReceptors, Prostaglandin E, EP4 SubtypeSignal TransductionSulfonamidesT-Lymphocytes, CytotoxicHepatic Acetyl CoA Links Adipose Tissue Inflammation to Hepatic Insulin Resistance and Type 2 Diabetes
Perry RJ, Camporez JP, Kursawe R, Titchenell PM, Zhang D, Perry CJ, Jurczak MJ, Abudukadier A, Han MS, Zhang XM, Ruan HB, Yang X, Caprio S, Kaech SM, Sul HS, Birnbaum MJ, Davis RJ, Cline GW, Petersen KF, Shulman GI. Hepatic Acetyl CoA Links Adipose Tissue Inflammation to Hepatic Insulin Resistance and Type 2 Diabetes. Cell 2015, 160: 745-758. PMID: 25662011, PMCID: PMC4498261, DOI: 10.1016/j.cell.2015.01.012.Peer-Reviewed Original ResearchConceptsHepatic glucose productionWhite adipose tissueHepatic insulin resistanceInsulin resistanceImpaired insulin-mediated suppressionAdipose tissue inflammationIL-6 neutralizationIL-6 infusionType 2 diabetesInsulin-mediated suppressionSuppression of lipolysisAdipose triglyceride lipaseTissue inflammationAdipose tissueType 2Fed ratsGlucose productionGenetic ablationInsulin's abilityAcetyl CoATriglyceride lipaseInsulin signalingRatsMetabolomics approachInsulin
2014
The Transcription Factor FoxO1 Sustains Expression of the Inhibitory Receptor PD-1 and Survival of Antiviral CD8+ T Cells during Chronic Infection
Staron MM, Gray SM, Marshall HD, Parish IA, Chen JH, Perry CJ, Cui G, Li MO, Kaech SM. The Transcription Factor FoxO1 Sustains Expression of the Inhibitory Receptor PD-1 and Survival of Antiviral CD8+ T Cells during Chronic Infection. Immunity 2014, 41: 802-814. PMID: 25464856, PMCID: PMC4270830, DOI: 10.1016/j.immuni.2014.10.013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BlockingAntibodies, MonoclonalCD28 AntigensCD8-Positive T-LymphocytesCell DifferentiationCell Line, TumorChronic DiseaseForkhead Box Protein O1Forkhead Transcription FactorsGranzymesHumansInterferon-gammaJurkat CellsLymphocyte ActivationLymphocytic ChoriomeningitisLymphocytic choriomeningitis virusMiceMice, Inbred C57BLMice, TransgenicProgrammed Cell Death 1 ReceptorProto-Oncogene Proteins c-aktReceptors, Antigen, T-CellSirolimusT-Lymphocytes, CytotoxicTOR Serine-Threonine KinasesConceptsChronic viral infectionsVirus-specific CTLPD-1Viral infectionMurine lymphocytic choriomeningitis virus infectionInhibitory receptor PD-1Lymphocytic choriomeningitis virus infectionCell death protein 1Receptor PD-1Death protein 1MTOR inhibitor rapamycinExhausted CTLsAntiviral CD8Activation of AktInhibitory receptorsTranscription factor FOXO1Chronic infectionT cellsT lymphocytesTherapeutic effectVirus infectionPersistent infectionPositive feedback pathwayInfectionCTLChronic viral infection promotes sustained Th1-derived immunoregulatory IL-10 via BLIMP-1
Parish IA, Marshall HD, Staron MM, Lang PA, Brüstle A, Chen JH, Cui W, Tsui YC, Perry C, Laidlaw BJ, Ohashi PS, Weaver CT, Kaech SM. Chronic viral infection promotes sustained Th1-derived immunoregulatory IL-10 via BLIMP-1. Journal Of Clinical Investigation 2014, 124: 3455-3468. PMID: 25003188, PMCID: PMC4109559, DOI: 10.1172/jci66108.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChronic DiseaseCytokinesInflammation MediatorsInterleukin-10Lymphocytic ChoriomeningitisLymphocytic choriomeningitis virusMAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicPositive Regulatory Domain I-Binding Factor 1Receptors, Antigen, T-CellTh1 CellsT-Lymphocyte SubsetsTranscription FactorsConceptsChronic viral infectionsIL-10 expressionT cell responsesIL-10 productionIL-10Th1 cellsViral infectionT cellsBlimp-1Viral-specific T cell responsesChronic lymphocytic choriomeningitis virus (LCMV) infectionAntiviral T cell responsesCell responsesImmunosuppressive cytokine IL-10Virus-specific T cellsLymphocytic choriomeningitis virus infectionChronic LCMV infectionImmunoregulatory IL-10Relevant cellular sourceCytokine IL-10Effector T cellsLCMV-infected micePersistent viral infectionT cell compartmentT cell function