2024
057 Single cell RNA and TCR sequencing reveals hyperexpansion of T cell clones and novel regulatory mechanisms of CD8+ T cells in murine alopcecia areata skin and draining lymph nodes
Wang Y, Yu W, Micevic G, Daccache J, Wang A, Park K, Wang G, Palmatier M, Wheeler J, King B, Damsky W. 057 Single cell RNA and TCR sequencing reveals hyperexpansion of T cell clones and novel regulatory mechanisms of CD8+ T cells in murine alopcecia areata skin and draining lymph nodes. Journal Of Investigative Dermatology 2024, 144: s10. DOI: 10.1016/j.jid.2024.06.073.Peer-Reviewed Original Research795 Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells
Bangert C, Alkon N, Chennareddy S, Arnoldner T, Levine J, Pilz M, Ruggiero J, Cohenour E, Jonak C, Damsky W, Griss J, Brunner P. 795 Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells. Journal Of Investigative Dermatology 2024, 144: s139. DOI: 10.1016/j.jid.2024.06.811.Peer-Reviewed Original ResearchDupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells
Bangert C, Alkon N, Chennareddy S, Arnoldner T, Levine J, Pilz M, Medjimorec M, Ruggiero J, Cohenour E, Jonak C, Damsky W, Griss J, Brunner P. Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells. Nature Communications 2024, 15: 2839. PMID: 38565563, PMCID: PMC10987549, DOI: 10.1038/s41467-024-46540-0.Peer-Reviewed Original ResearchConceptsHead and neck dermatitisAtopic dermatitisNeck dermatitisT cellsHealthy control skinType 2 inflammationDupilumab treatmentImmune signaturesReceptor upregulationActivation markersClinical efficacyPunch biopsyHistopathological featuresDe novo appearanceIL-22Single-cell RNA sequencingDrug effectsDupilumabSide effectsControl skinDermatitisKeratinocyte activationUntreated ADTreatmentRNA sequencing
2023
Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part I. Epidemiology, pathogenesis, clinicopathological features, and prognosis
Wei B, Fox L, Kaffenberger B, Korman A, Micheletti R, Mostaghimi A, Noe M, Rosenbach M, Shinkai K, Kwah J, Phillips E, Bolognia J, Damsky W, Nelson C. Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part I. Epidemiology, pathogenesis, clinicopathological features, and prognosis. Journal Of The American Academy Of Dermatology 2023, 90: 885-908. PMID: 37516359, DOI: 10.1016/j.jaad.2023.02.072.Peer-Reviewed Original ResearchSevere cutaneous adverse reactionsDiHS/DRESSClinicopathological featuresSystemic symptomsDrug reactionsDrug-induced hypersensitivity syndrome/drug reactionDrug-induced hypersensitivity syndromePart I. EpidemiologyVisceral organ involvementCutaneous adverse reactionsRisk of relapseHypersensitivity syndromeOrgan involvementI. EpidemiologyOrgan dysfunctionSignificant morbidityAutoimmune diseasesAdverse reactionsDrug exposureT cellsCommon triggerImmune systemPathogenesisEosinophiliaMedical education activitiesCombinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.
Krykbaeva I, Bridges K, Damsky W, Pizzurro G, Alexander A, McGeary M, Park K, Muthusamy V, Eyles J, Luheshi N, Turner N, Weiss S, Olino K, Kaech S, Kluger H, Miller-Jensen K, Bosenberg M. Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance. Cancer Immunology Research 2023, 11: 1332-1350. PMID: 37478171, DOI: 10.1158/2326-6066.cir-22-0699.Peer-Reviewed Original ResearchConceptsPD-1 resistanceDendritic cellsTumor regressionAnti-PD-1 resistanceActivates Dendritic CellsCytokine secretion profilingSystemic cytokine profileTriple therapy combinationInnate immune activationAdaptive immune responsesComplete tumor regressionMajority of miceSignificant clinical challengeMouse melanoma modelT cell activationAgonistic CD40Checkpoint inhibitorsDC subsetsTriple therapyCytokine profileImmune activationCombinatorial immunotherapyTherapy combinationsT cellsClinical challengePD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens
Damo M, Hornick N, Venkat A, William I, Clulo K, Venkatesan S, He J, Fagerberg E, Loza J, Kwok D, Tal A, Buck J, Cui C, Singh J, Damsky W, Leventhal J, Krishnaswamy S, Joshi N. PD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens. Nature 2023, 619: 151-159. PMID: 37344588, PMCID: PMC10989189, DOI: 10.1038/s41586-023-06217-y.Peer-Reviewed Original ResearchConceptsEffector CD8 T cellsCD8 T cellsAntigen-specific effector CD8 T cellsAntigen-specific CD8 T cellsAntigen-expressing cellsT cell tolerancePD-1T cellsAdverse eventsCell toleranceCD8 T cell toleranceImmune-related adverse eventsPeripheral T cell repertoirePeripheral T cell toleranceNon-lesional skinT cell repertoireT-cell antigensPeripheral toleranceCheckpoint receptorsSkin biopsiesLocal infiltrationLocal pathologyCell repertoireMouse modelSkin toleranceIntegrated transcriptome and trajectory analysis of cutaneous T-cell lymphoma identifies putative precancer populations
Ren J, Qu R, Rahman N, Lewis J, King A, Liao X, Mirza F, Carlson K, Huang Y, Gigante S, Evans B, Rajendran B, Xu S, Wang G, Foss F, Damsky W, Kluger Y, Krishnaswamy S, Girardi M. Integrated transcriptome and trajectory analysis of cutaneous T-cell lymphoma identifies putative precancer populations. Blood Advances 2023, 7: 445-457. PMID: 35947128, PMCID: PMC9979716, DOI: 10.1182/bloodadvances.2022008168.Peer-Reviewed Original ResearchConceptsCutaneous T-cell lymphomaMalignant CTCL cellsDiverse transcriptomic profilesT cellsSingle-cell RNACTCL cellsDevelopment of CTCLIntegrated transcriptomeT-cell receptor sequencingT cell exhaustion phenotypeCommon antigenic stimulusPeripheral blood CD4Transcriptomic profilesGene expressionT-cell lymphomaIntegrative analysisPotential therapeutic targetProliferation advantageLimited diversityBlood CD4Blood involvementMutation levelsExhaustion phenotypeWorse prognosisAntigenic stimulus
2020
IL-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
2017
UV‐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