2019
Tumor regression mediated by oncogene withdrawal or erlotinib stimulates infiltration of inflammatory immune cells in EGFR mutant lung tumors
Ayeni D, Miller B, Kuhlmann A, Ho PC, Robles-Oteiza C, Gaefele M, Levy S, de Miguel FJ, Perry C, Guan T, Krystal G, Lockwood W, Zelterman D, Homer R, Liu Z, Kaech S, Politi K. Tumor regression mediated by oncogene withdrawal or erlotinib stimulates infiltration of inflammatory immune cells in EGFR mutant lung tumors. Journal For ImmunoTherapy Of Cancer 2019, 7: 172. PMID: 31291990, PMCID: PMC6617639, DOI: 10.1186/s40425-019-0643-8.Peer-Reviewed Original ResearchConceptsTyrosine kinase inhibitorsEGFR-mutant lung cancerMutant lung cancerTumor regressionErlotinib treatmentLung cancerImmune cellsLung tumorsMouse modelEffects of TKIsGrowth factor receptor tyrosine kinase inhibitorsTumor-infiltrating immune cellsDrug resistanceReceptor tyrosine kinase inhibitorsInflammatory immune cellsInflammatory T cellsEffect of erlotinibEGFR mutant lung tumorsInflammatory cellsImmunological profileT cellsCD40 agonistsImmunostimulatory effectsAlveolar macrophagesErlotinib
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 turnoverCellsUV‐induced somatic mutations elicit a functional T cell response in the YUMMER1.7 mouse melanoma model
Wang J, Perry CJ, Meeth K, Thakral D, Damsky W, Micevic G, Kaech S, Blenman K, Bosenberg M. UV‐induced somatic mutations elicit a functional T cell response in the YUMMER1.7 mouse melanoma model. Pigment Cell & Melanoma Research 2017, 30: 428-435. PMID: 28379630, PMCID: PMC5820096, DOI: 10.1111/pcmr.12591.Peer-Reviewed Original ResearchConceptsHigh somatic mutation burdenSomatic mutation burdenT cellsMutation burdenAnti-PD-1 therapyFunctional T cell responsesImmune checkpoint inhibitionAntitumor immune responseCD8 T cellsT cell responsesMouse melanoma modelCell numberSomatic mutationsMouse melanoma cell lineMelanoma cell linesTumor challengeAntitumor responseCheckpoint inhibitionImmune responseMelanoma modelHigh dosesImmune systemCell responsesMelanomas exhibitTumors
2016
CCR7 expression alters memory CD8 T-cell homeostasis by regulating occupancy in IL-7– and IL-15–dependent niches
Jung YW, Kim HG, Perry CJ, Kaech SM. CCR7 expression alters memory CD8 T-cell homeostasis by regulating occupancy in IL-7– and IL-15–dependent niches. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 8278-8283. PMID: 27385825, PMCID: PMC4961181, DOI: 10.1073/pnas.1602899113.Peer-Reviewed Original ResearchConceptsC receptor 7Memory T cellsMemory CD8 T-cell homeostasisMemory CD8 T cellsCD8 T cell homeostasisCD8 T cellsT cellsT cell homeostasisIL-15IL-7Different memory T-cell subsetsMemory CD8 T cell poolCD8 T cell poolLymphocytic choriomeningitis virus infectionMemory T cell subsetsHomeostasis of effectorAcute viral infectionT cell poolT cell subsetsT cell zonesDendritic cellsLymph nodesPredominant cytokineReceptor 7Chemokine receptors
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, Cytotoxic
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