2021
Chronic UV radiation–induced RORγt+ IL-22–producing lymphoid cells are associated with mutant KC clonal expansion
Lewis JM, Monico PF, Mirza FN, Xu S, Yumeen S, Turban JL, Galan A, Girardi M. Chronic UV radiation–induced RORγt+ IL-22–producing lymphoid cells are associated with mutant KC clonal expansion. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2016963118. PMID: 34504008, PMCID: PMC8449378, DOI: 10.1073/pnas.2016963118.Peer-Reviewed Original ResearchConceptsChronic UV exposureLangerhans cellsIL-22Cutaneous carcinogenesisCutaneous squamous cell carcinoma (cSCC) developmentChronic ultraviolet radiation exposureSquamous cell carcinoma developmentClonal expansionEpidermal Langerhans cellsToll-like receptorsSkin cancer preventionGreatest risk factorDouble-deficient miceUltraviolet radiation exposureKey immune componentsImmune shiftKC growthIL-17ARisk factorsCancer preventionT cellsImmune responseCarcinoma developmentIntracellular CD3Immune componentsNonsurgical treatment of skin cancer with local delivery of bioadhesive nanoparticles
Hu JK, Suh HW, Qureshi M, Lewis JM, Yaqoob S, Moscato ZM, Griff S, Lee AK, Yin ES, Saltzman WM, Girardi M. Nonsurgical treatment of skin cancer with local delivery of bioadhesive nanoparticles. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2020575118. PMID: 33526595, PMCID: PMC7896333, DOI: 10.1073/pnas.2020575118.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaNonsurgical treatmentSkin cancerTumor cell surfaceIntratumoral drug deliveryHistologic cureCutaneous malignanciesSurgical excisionTherapeutic standardTumor burdenTumor immunotherapyTumor injectionCommon malignancyCell carcinomaSCC tumorsNonsurgical alternativeTherapeutic efficacyD postinjectionNanoparticle drug delivery systemsChemotherapeutic agentsSuperficial tumorsTumorsLocal deliveryEnhanced survivalPercutaneous delivery
2020
Research Techniques Made Simple: Preclinical Development of Combination Antitumor Targeted Therapies in Dermatology
Yumeen S, Mirza FN, Lewis JM, Girardi M. Research Techniques Made Simple: Preclinical Development of Combination Antitumor Targeted Therapies in Dermatology. Journal Of Investigative Dermatology 2020, 140: 2319-2325.e1. PMID: 33222758, DOI: 10.1016/j.jid.2020.09.020.Peer-Reviewed Original ResearchConceptsCombination regimensCutaneous malignanciesMalignant cellsRelevant mouse modelPotential synergistic combinationsAdvanced cutaneous malignanciesClinical trial designChou-Talalay methodCancer cell linesClinical outcomesTherapy regimensDefinitive cureTargeted therapyTumor cell heterogeneityDrug combinationsMouse modelTrial designPreclinical developmentDrug resistanceRegimensCombination indexSynergistic activityOff-target effectsCritical pathwaysCell lines
2018
Extracorporeal Photochemotherapy Drives Monocyte-to-Dendritic Cell Maturation to Induce Anti-Cancer Immunity
Ventura A, Vassall A, Robinson E, Filler R, Hanlon D, Meeth K, Ezaldein H, Girardi M, Sobolev O, Bosenberg MW, Edelson RL. Extracorporeal Photochemotherapy Drives Monocyte-to-Dendritic Cell Maturation to Induce Anti-Cancer Immunity. Cancer Research 2018, 78: canres.0171.2018. PMID: 29764863, DOI: 10.1158/0008-5472.can-18-0171.Peer-Reviewed Original ResearchConceptsT cellsT cell antitumor immunityTumor-specific T cellsTumor cellsEffective immunotherapeutic agentFavorable safety profileResponder T cellsDendritic cell differentiationTumor-challenged miceImmunogenic cell deathSelective antitumor effectApoptotic tumor cellsPotential therapeutic applicabilityProcessing/presentationAntimelanoma immunityHealthy DCsImmunogenic malignanciesAntitumor immunityCellular vaccinesImmunotherapeutic effectsAdditional malignanciesImmunotherapeutic agentsSafety profileCancer immunotherapyTumor antigensCommensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus
Greiling TM, Dehner C, Chen X, Hughes K, Iñiguez AJ, Boccitto M, Ruiz DZ, Renfroe SC, Vieira SM, Ruff WE, Sim S, Kriegel C, Glanternik J, Chen X, Girardi M, Degnan P, Costenbader KH, Goodman AL, Wolin SL, Kriegel MA. Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus. Science Translational Medicine 2018, 10 PMID: 29593104, PMCID: PMC5918293, DOI: 10.1126/scitranslmed.aan2306.Peer-Reviewed Original ResearchConceptsLupus patientsGlomerular immune complex depositsPositive lupus patientsImmune complex depositsGerm-free miceSigns of autoimmunityB cell responsesT cell clonesNovel treatment approachesTriggers of autoimmunityCommensal bacterial speciesEarliest autoantibodiesChronic autoimmunityAutoimmune diseasesHealthy controlsT cellsTreatment approachesSusceptible individualsAutoimmunityCell responsesCommensal speciesLupusPatientsCell clonesGut commensals
2015
A sunblock based on bioadhesive nanoparticles
Deng Y, Ediriwickrema A, Yang F, Lewis J, Girardi M, Saltzman WM. A sunblock based on bioadhesive nanoparticles. Nature Materials 2015, 14: 1278-1285. PMID: 26413985, PMCID: PMC4654636, DOI: 10.1038/nmat4422.Peer-Reviewed Original ResearchConceptsBioadhesive nanoparticlesCommercial sunscreen formulationsInorganic ultraviolet (UV) filtersUV filtersCellular exposureCutaneous phototoxicityMurine modelFollicular penetrationHealth concernNanoparticlesUV filter concentrationsTowel dryingPadimate OUV protectionSunblockSunscreen formulationsStratum corneumUltraviolet filtersExposureFilterLangerhans Cells Facilitate UVB-Induced Epidermal Carcinogenesis
Lewis JM, Bürgler CD, Freudzon M, Golubets K, Gibson JF, Filler RB, Girardi M. Langerhans Cells Facilitate UVB-Induced Epidermal Carcinogenesis. Journal Of Investigative Dermatology 2015, 135: 2824-2833. PMID: 26053049, PMCID: PMC4640962, DOI: 10.1038/jid.2015.207.Peer-Reviewed Original ResearchConceptsLangerhans cellsGroup 3 innate lymphoid cellsAbsence of LCsRole of LCsSquamous cell carcinoma formationInnate lymphoid cellsUVB-induced carcinogenesisInnate immune cellsAcute UVB exposureT-cell independentTumor suppressor gene p53IL-22Cutaneous carcinogenesisImmune cellsTumor outgrowthKC populationLymphoid cellsChronic exposureKC proliferationUVB exposureCarcinoma formationClonal expansionEpidermal carcinogenesisGene p53Carcinogenesis
2014
Mechanisms of Chemical Cooperative Carcinogenesis by Epidermal Langerhans Cells
Lewis JM, Bürgler CD, Fraser JA, Liao H, Golubets K, Kucher CL, Zhao PY, Filler RB, Tigelaar RE, Girardi M. Mechanisms of Chemical Cooperative Carcinogenesis by Epidermal Langerhans Cells. Journal Of Investigative Dermatology 2014, 135: 1405-1414. PMID: 25233073, PMCID: PMC4364923, DOI: 10.1038/jid.2014.411.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaLC-deficient miceLangerhans cellsPresence of LCCutaneous squamous cell carcinomaEpidermal Langerhans cellsMyeloid-derived cellsEnzyme CYP1B1Infundibular keratinocytesDendritic cellsCell carcinomaInvasive malignancyCutaneous carcinogenesisCarcinogenesis roleTobacco smokeLC precursorsMalignant transformationTumor progressionMetastatic potentialTumor susceptibilityMiceChemical carcinogenesisCarcinogenesisNeoplastic transformationLC expressionIL-9 Regulates Allergen-Specific Th1 Responses in Allergic Contact Dermatitis
Liu J, Harberts E, Tammaro A, Girardi N, Filler RB, Fishelevich R, Temann A, Licona-Limón P, Girardi M, Flavell RA, Gaspari AA. IL-9 Regulates Allergen-Specific Th1 Responses in Allergic Contact Dermatitis. Journal Of Investigative Dermatology 2014, 134: 1903-1911. PMID: 24487305, PMCID: PMC4303591, DOI: 10.1038/jid.2014.61.Peer-Reviewed Original ResearchConceptsAllergic contact dermatitisIL-9 productionIL-9IL-4Contact dermatitisAllergen-specific Th1 responsesHuman allergic contact dermatitisPositive patch test sitesPeripheral blood mononuclear cellsCytokine IL-9Non-atopic patientsContact hypersensitivity modelIFN-γ productionIL-4 secretionBlood mononuclear cellsNickel-allergic patientsLymphocyte immune responseSkin biopsy specimensWild-type micePatch test sitesTh9 lymphocytesAllergic asthmaIL-17ATh1 responseCytokines IFN
2012
Langerhans Cells Facilitate Epithelial DNA Damage and Squamous Cell Carcinoma
Modi BG, Neustadter J, Binda E, Lewis J, Filler RB, Roberts SJ, Kwong BY, Reddy S, Overton JD, Galan A, Tigelaar R, Cai L, Fu P, Shlomchik M, Kaplan DH, Hayday A, Girardi M. Langerhans Cells Facilitate Epithelial DNA Damage and Squamous Cell Carcinoma. Science 2012, 335: 104-108. PMID: 22223807, PMCID: PMC3753811, DOI: 10.1126/science.1211600.Peer-Reviewed Original ResearchMeSH Keywords9,10-Dimethyl-1,2-benzanthraceneAnimalsAryl Hydrocarbon HydroxylasesCarcinogensCarcinoma, Squamous CellCell Transformation, NeoplasticCells, CulturedCytochrome P-450 CYP1A1Cytochrome P-450 CYP1B1DNA DamageGenes, rasHumansKeratinocytesLangerhans CellsMiceMice, TransgenicSkin NeoplasmsT-LymphocytesConceptsLangerhans cellsDendritic cellsDMBA-induced DNA damageCutaneous chemical carcinogenesisEpidermal dendritic cellsLC-deficient miceT cell immunitySquamous cell carcinomaChemical carcinogenesisDMBA-transHras mutationsCell immunityCell carcinomaImmune cellsDNA damageTumor resistanceDMBAPrior incubationHuman keratinocytesCarcinogenesisUnderlying mechanismMicePotent carcinogenSkinPAH metabolism
2009
Molecular Analysis of Tumor-Promoting CD8+ T Cells in Two-Stage Cutaneous Chemical Carcinogenesis
Kwong BY, Roberts SJ, Silberzahn T, Filler RB, Neustadter JH, Galan A, Reddy S, Lin WM, Ellis PD, Langford CF, Hayday AC, Girardi M. Molecular Analysis of Tumor-Promoting CD8+ T Cells in Two-Stage Cutaneous Chemical Carcinogenesis. Journal Of Investigative Dermatology 2009, 130: 1726-1736. PMID: 19924136, PMCID: PMC2920801, DOI: 10.1038/jid.2009.362.Peer-Reviewed Original ResearchMeSH Keywords9,10-Dimethyl-1,2-benzanthraceneAmphiregulinAnimalsCD8-Positive T-LymphocytesCell DifferentiationDisease Models, AnimalEGF Family of ProteinsForkhead Transcription FactorsGene Expression ProfilingGlycoproteinsHepatitis A Virus Cellular Receptor 2Intercellular Signaling Peptides and ProteinsInterleukin-10Interleukin-17MiceMice, KnockoutReceptors, Antigen, T-Cell, alpha-betaReceptors, VirusSkin NeoplasmsConceptsTumor-infiltrating lymphocytesT cellsCutaneous carcinogenesisIL-17-producing T cellsT-proCutaneous chemical carcinogenesisTricolor flow cytometryContribution of inflammationCytolytic T cellsTumor-bearing miceEpithelial growth factorMechanism of actionT helperCancer immunotherapyUseful biomarkerMalignant progressionFlow cytometryClear associationGrowth factorReduced cytotoxicChemical carcinogenesisCarcinogenesisPro phenotypeWhole genome expression analysisTime-course analysisCD27 is a thymic determinant of the balance between interferon-γ- and interleukin 17–producing γδ T cell subsets
Ribot JC, deBarros A, Pang DJ, Neves JF, Peperzak V, Roberts SJ, Girardi M, Borst J, Hayday AC, Pennington DJ, Silva-Santos B. CD27 is a thymic determinant of the balance between interferon-γ- and interleukin 17–producing γδ T cell subsets. Nature Immunology 2009, 10: 427-436. PMID: 19270712, PMCID: PMC4167721, DOI: 10.1038/ni.1717.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD27 LigandCells, CulturedInterferon-gammaInterleukin-17Lymphoid Progenitor CellsLymphotoxin beta ReceptorMalaria, CerebralMiceMice, Inbred C57BLPlasmodium bergheiReceptors, Antigen, T-Cell, gamma-deltaThymus GlandT-Lymphocyte SubsetsTumor Necrosis Factor Receptor Superfamily, Member 7
2008
Skint1, the prototype of a newly identified immunoglobulin superfamily gene cluster, positively selects epidermal γδ T cells
Boyden LM, Lewis JM, Barbee SD, Bas A, Girardi M, Hayday AC, Tigelaar RE, Lifton RP. Skint1, the prototype of a newly identified immunoglobulin superfamily gene cluster, positively selects epidermal γδ T cells. Nature Genetics 2008, 40: 656-662. PMID: 18408721, PMCID: PMC4167720, DOI: 10.1038/ng.108.Peer-Reviewed Original ResearchCutaneous T cell lymphoma: translating immunobiology into therapeutic opportunities.
Berger CL, Heald P, Girardi M, Edelson RL. Cutaneous T cell lymphoma: translating immunobiology into therapeutic opportunities. Giornale Italiano Di Dermatologia E Venereologia 2008, 143: 43-54. PMID: 18833050.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal Cortex HormonesAnimalsAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsApoptosisBexaroteneClone CellsCytokinesDendritic CellsDiphtheria ToxinGene Expression Regulation, NeoplasticHumansImmunophenotypingInterleukin-2Lymphoma, T-Cell, CutaneousMiceNeoplastic Stem CellsPhotopheresisPUVA TherapyRecombinant Fusion ProteinsTetrahydronaphthalenesT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryConceptsCutaneous T-cell lymphomaSheep red blood cellsT-cell lymphomaNew therapeutic approachesBasic science techniquesRed blood cellsClinical featuresTherapeutic optionsT lymphocytesCell lymphomaTherapeutic approachesClinical practiceImmune systemMalignant cellsTherapeutic opportunitiesBlood cellsPatientsImmunobiologyDiseaseMolecular demonstrationCurrent understandingCellsLymphomaLymphocytesImmunologyAcute upregulation of an NKG2D ligand promotes rapid reorganization of a local immune compartment with pleiotropic effects on carcinogenesis
Strid J, Roberts SJ, Filler RB, Lewis JM, Kwong BY, Schpero W, Kaplan DH, Hayday AC, Girardi M. Acute upregulation of an NKG2D ligand promotes rapid reorganization of a local immune compartment with pleiotropic effects on carcinogenesis. Nature Immunology 2008, 9: 146-154. PMID: 18176566, DOI: 10.1038/ni1556.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Transformation, NeoplasticEpidermisHistocompatibility Antigens Class IImmunologic SurveillanceLangerhans CellsLigandsMiceMice, Inbred StrainsNK Cell Lectin-Like Receptor Subfamily KReceptors, Antigen, T-Cell, alpha-betaReceptors, Antigen, T-Cell, gamma-deltaReceptors, ImmunologicReceptors, Natural Killer CellSkin NeoplasmsT-LymphocytesUp-RegulationConceptsNKG2D ligandsImmune compartmentLangerhans cellsT cellsRAE-1Local immune compartmentIntraepithelial T cellsΑβ T cellsEpithelial infiltrationTissue immunosurveillanceGraft rejectionInflammatory lesionsReceptor NKG2DAcute changesLigand MICACytotoxic lymphocytesAcute upregulationImmunosurveillanceEarly phaseCarcinogenesisUpregulationPleiotropic effectsCellsNKG2DCarcinoma
2007
Characterizing tumor-promoting T cells in chemically induced cutaneous carcinogenesis
Roberts SJ, Ng BY, Filler RB, Lewis J, Glusac EJ, Hayday AC, Tigelaar RE, Girardi M. Characterizing tumor-promoting T cells in chemically induced cutaneous carcinogenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 6770-6775. PMID: 17412837, PMCID: PMC1871860, DOI: 10.1073/pnas.0604982104.Peer-Reviewed Original ResearchConceptsT cell deficiencyT cellsCell deficiencyPRO cellsCell-deficient miceTumor-infiltrating lymphocytesAnti-tumor responseT cell populationsInflammation-associated carcinogenesisT cell receptorImmunotherapeutic strategiesRegulatory cellsCancer immunosurveillanceCell reconstitutionEpidemiologic linkCutaneous carcinogenesisTumor incidenceCyclooxygenase-2Activated populationCell receptorNovel populationCell populationsChemical carcinogenesisCarcinogenesisLymphocytesPromotion of Hras-induced squamous carcinomas by a polymorphic variant of the Patched gene in FVB mice
Wakabayashi Y, Mao JH, Brown K, Girardi M, Balmain A. Promotion of Hras-induced squamous carcinomas by a polymorphic variant of the Patched gene in FVB mice. Nature 2007, 445: 761-765. PMID: 17230190, DOI: 10.1038/nature05489.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsApoptosisCarcinoma, Squamous CellCell LineCell Transformation, NeoplasticCrosses, GeneticFemaleGene Expression Regulation, NeoplasticGenes, rasHSP40 Heat-Shock ProteinsHumansKruppel-Like Transcription FactorsMaleMiceMice, Inbred C57BLMice, TransgenicMolecular Sequence DataPatched ReceptorsPatched-1 ReceptorPolymorphism, GeneticRas ProteinsReceptors, Cell SurfaceZinc Finger Protein Gli2ConceptsSquamous carcinomaTumor suppressor geneFVB/N miceSonic hedgehogSuppressor geneFVB/N strainBasal cell carcinomaPTCH geneSame target cellsCell lineage commitmentPatched geneHuman patched geneHost genetic backgroundClassical tumor suppressor geneCell carcinomaPtch alleleFVB miceN miceCarcinogen exposureC57BL/6 strainTumor typesLineage commitmentMouse homologueHybrid miceGenetic basis
2006
Selection of the cutaneous intraepithelial γδ+ T cell repertoire by a thymic stromal determinant
Lewis JM, Girardi M, Roberts SJ, D Barbee S, Hayday AC, Tigelaar RE. Selection of the cutaneous intraepithelial γδ+ T cell repertoire by a thymic stromal determinant. Nature Immunology 2006, 7: 843-850. PMID: 16829962, DOI: 10.1038/ni1363.Peer-Reviewed Original ResearchConceptsT cellsIntraepithelial lymphocytesT cell receptorMouse dendritic epidermal T-cellsOligoclonal T-cell receptorsDendritic epidermal T cellsEpidermal T cellsT cell repertoireT cell progenitorsCutaneous pathologyCell repertoireThymic stromaStromal determinantsLymphocyte repertoireCell receptorLymphocytesCell progenitorsHeritable defectsCellsIntraepithelialAgonistsMicePathologyPhysiological useStromaEnvironmentally Responsive and Reversible Regulation of Epidermal Barrier Function by γδ T Cells
Girardi M, Lewis JM, Filler RB, Hayday AC, Tigelaar RE. Environmentally Responsive and Reversible Regulation of Epidermal Barrier Function by γδ T Cells. Journal Of Investigative Dermatology 2006, 126: 808-814. PMID: 16439970, DOI: 10.1038/sj.jid.5700120.Peer-Reviewed Original ResearchConceptsDendritic epidermal T cellsT cellsGammadelta T cell-deficient miceLimited T cell receptor diversityT cell-deficient miceBarrier functionTCRdelta-/- miceT-cell receptor diversityEpidermal T cellsT cell compartmentΓδ T cellsBarrier function defectsEpidermal barrier functionTransepidermal water lossPathogen-specific antigensCutaneous inflammationCutaneous neoplasiaDeficient miceGammadelta cellsFunction defectsCutaneous physiologyFetal thymocytesEpidermal barrierHydration statusReceptor diversityImmunosurveillance and Immunoregulation by γδ T Cells
Girardi M. Immunosurveillance and Immunoregulation by γδ T Cells. Journal Of Investigative Dermatology 2006, 126: 25-31. PMID: 16417214, DOI: 10.1038/sj.jid.5700003.Peer-Reviewed Original ResearchConceptsGammadelta T cellsT cell receptorT cellsGammadelta T-cell receptorΓδ T cellsCellular stressHuman diseasesAlphabeta heterodimersTCR diversityCutaneous functionImmunoregulatory activitySmall populationMutant miceEpithelial surfaceCellsHeterodimersVast majorityDiversityImmunosurveillanceImmunoregulation