2022
Inhibition of type 1 immunity with tofacitinib is associated with marked improvement in longstanding sarcoidosis
Damsky W, Wang A, Kim DJ, Young BD, Singh K, Murphy MJ, Daccache J, Clark A, Ayasun R, Ryu C, McGeary MK, Odell ID, Fazzone-Chettiar R, Pucar D, Homer R, Gulati M, Miller EJ, Bosenberg M, Flavell RA, King B. Inhibition of type 1 immunity with tofacitinib is associated with marked improvement in longstanding sarcoidosis. Nature Communications 2022, 13: 3140. PMID: 35668129, PMCID: PMC9170782, DOI: 10.1038/s41467-022-30615-x.Peer-Reviewed Original ResearchConceptsType 1 immunityInternal organ involvementOrgan involvementT cell-derived IFNIdiopathic inflammatory disorderOpen-label trialMonths of treatmentType 1 cytokinesJanus kinase inhibitorImmunologic changesLongstanding sarcoidosisSarcoidosis activitySarcoidosis symptomsClinical improvementCutaneous sarcoidosisSecondary outcomesComplete responsePrimary outcomeTofacitinib treatmentActivity scoreCytokine mediatorsIL-12IL-15IL-6Inflammatory disorders
2020
Treatment of granuloma annulare and suppression of proinflammatory cytokine activity with tofacitinib
Wang A, Rahman NT, McGeary MK, Murphy M, McHenry A, Peterson D, Bosenberg M, Flavell RA, King B, Damsky W. Treatment of granuloma annulare and suppression of proinflammatory cytokine activity with tofacitinib. Journal Of Allergy And Clinical Immunology 2020, 147: 1795-1809. PMID: 33317858, DOI: 10.1016/j.jaci.2020.10.012.Peer-Reviewed Original ResearchConceptsGranuloma annulareIL-15Oncostatin MT cellsEffective treatmentOpen-label clinical trialSingle-cell RNA sequencingEfficacy of tofacitinibIL-21 productionCutaneous inflammatory disordersIFN-γ productionJanus kinase inhibitorProinflammatory cytokine activityActivity of IFNGA pathogenesisIL-6 family cytokinesDisease remissionClinical improvementSystemic inflammationIL-21RNA sequencingMacrophage accumulationInflammatory disordersInflammatory polarizationClinical trialsIL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy
Zhou T, Damsky W, Weizman OE, McGeary MK, Hartmann KP, Rosen CE, Fischer S, Jackson R, Flavell RA, Wang J, Sanmamed MF, Bosenberg MW, Ring AM. IL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy. Nature 2020, 583: 609-614. PMID: 32581358, PMCID: PMC7381364, DOI: 10.1038/s41586-020-2422-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesDisease Models, AnimalFemaleHepatocyte Nuclear Factor 1-alphaHistocompatibility Antigens Class IHumansImmunotherapyIntercellular Signaling Peptides and ProteinsInterleukin-18Kaplan-Meier EstimateKiller Cells, NaturalLymphocytes, Tumor-InfiltratingMaleMiceNeoplasmsReceptors, Interleukin-18Stem CellsTumor MicroenvironmentConceptsIL-18IL-18BPT cellsAnti-PD-1 resistant tumorsWild-type IL-18Potent anti-tumor effectsMajor histocompatibility complex class IIL-18 pathwayIL-18 therapyInterleukin-18 pathwayMajor therapeutic barrierStem-like TCF1Anti-tumor immunityTumor-infiltrating lymphocytesNatural killer cellsRecombinant IL-18Histocompatibility complex class IAnti-tumor effectsComplex class IAnti-tumor activityMouse tumor modelsModern immunotherapyPrecursor CD8Effector CD8Exhausted CD8
2019
Janus kinase inhibition induces disease remission in cutaneous sarcoidosis and granuloma annulare
Damsky W, Thakral D, McGeary MK, Leventhal J, Galan A, King B. Janus kinase inhibition induces disease remission in cutaneous sarcoidosis and granuloma annulare. Journal Of The American Academy Of Dermatology 2019, 82: 612-621. PMID: 31185230, PMCID: PMC7590533, DOI: 10.1016/j.jaad.2019.05.098.Peer-Reviewed Original ResearchConceptsGranuloma annulareCutaneous sarcoidosisPathway activationCutaneous granulomatous disordersRecalcitrant cutaneous sarcoidosisSkin biopsy specimensSignal regulatory protein αJAK-STAT pathway activationTranscription (JAK/STAT) pathway activationRegulatory protein αRecalcitrant sarcoidosisSarcoidosis activityDisease remissionConsecutive patientsGranulomatous disorderProspective evaluationBiopsy specimensHistologic resolutionSkin biopsiesMean improvementSarcoidosisImmunohistochemical analysisJAK inhibitorsJAK inhibitionPatientsKDM5B Promotes Drug Resistance by Regulating Melanoma Propagating Cell Subpopulations
Liu X, Zhang SM, McGeary MK, Krykbaeva I, Lai L, Jansen DJ, Kales SC, Simeonov A, Hall MD, Kelly DP, Bosenberg MW, Yan Q. KDM5B Promotes Drug Resistance by Regulating Melanoma Propagating Cell Subpopulations. Molecular Cancer Therapeutics 2019, 18: molcanther.0395.2018. PMID: 30523048, PMCID: PMC6397704, DOI: 10.1158/1535-7163.mct-18-0395.Peer-Reviewed Original Research
2018
PD‐L1 methylation regulates PD‐L1 expression and is associated with melanoma survival
Micevic G, Thakral D, McGeary M, Bosenberg M. PD‐L1 methylation regulates PD‐L1 expression and is associated with melanoma survival. Pigment Cell & Melanoma Research 2018, 32: 435-440. PMID: 30343532, PMCID: PMC6475614, DOI: 10.1111/pcmr.12745.Peer-Reviewed Original ResearchConceptsPD-L1 expressionDNA methylationPD-1/PD-L1 immune checkpointIndependent survival prognostic factorPD-L1 promoter methylationPD-L1 immune checkpointSurvival prognostic factorsPD-L1 promoterPromoter DNA methylationOverall survivalImmune checkpointsPrognostic factorsMelanoma patientsMelanoma survivalEpigenetic mechanismsTranscriptional phenotypeClinical importanceMelanomaCpG lociMethylationPromoter methylationSurvivalTherapeutic applicationsExpressionPatients