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