2023
Combinatorial 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 challengePTEN phosphatase inhibits metastasis by negatively regulating the Entpd5/IGF1R pathway through ATF6
Yu Y, Dai M, Huang L, Chen W, Yu E, Mendoza A, Michael H, Khanna C, Bosenberg M, McMahon M, Merlino G. PTEN phosphatase inhibits metastasis by negatively regulating the Entpd5/IGF1R pathway through ATF6. IScience 2023, 26: 106070. PMID: 36824269, PMCID: PMC9942123, DOI: 10.1016/j.isci.2023.106070.Peer-Reviewed Original ResearchProtein phosphatase activityPhosphatase activityPTEN protein phosphatase activityER stress sensor ATF6ER stressPTEN phosphatase activityPTEN expressionMelanoma cell invasivenessNovel candidate therapeutic targetInhibits metastasisIGF1R pathwayIGF1R levelsHuman melanoma samplesTumor suppressorCandidate therapeutic targetCell invasivenessATF6Melanoma samplesMetastatic progressionTherapeutic targetExpressionDose-dependent mannerPathwayMouse melanoma modelMutant melanoma
2021
KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements
Zhang SM, Cai WL, Liu X, Thakral D, Luo J, Chan LH, McGeary MK, Song E, Blenman KRM, Micevic G, Jessel S, Zhang Y, Yin M, Booth CJ, Jilaveanu LB, Damsky W, Sznol M, Kluger HM, Iwasaki A, Bosenberg MW, Yan Q. KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements. Nature 2021, 598: 682-687. PMID: 34671158, PMCID: PMC8555464, DOI: 10.1038/s41586-021-03994-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorDNA-Binding ProteinsEpigenesis, GeneticGene SilencingHeterochromatinHistone-Lysine N-MethyltransferaseHumansInterferon Type IJumonji Domain-Containing Histone DemethylasesMaleMelanomaMiceMice, Inbred C57BLMice, KnockoutNuclear ProteinsRepressor ProteinsRetroelementsTumor EscapeConceptsImmune checkpoint blockadeImmune evasionCheckpoint blockadeImmune responseAnti-tumor immune responseRobust adaptive immune responseTumor immune evasionAnti-tumor immunityAdaptive immune responsesType I interferon responseDNA-sensing pathwayMouse melanoma modelImmunotherapy resistanceMost patientsCurrent immunotherapiesTumor immunogenicityImmune memoryMelanoma modelCytosolic RNA sensingRole of KDM5BConsiderable efficacyInterferon responseImmunotherapyEpigenetic therapyBlockade
2020
The role of CD36 in macrophage lipid metabolism and function in tumor microenvironment
Xu Z, Xu S, Kuhlmann A, Kaech S. The role of CD36 in macrophage lipid metabolism and function in tumor microenvironment. The Journal Of Immunology 2020, 204: 240.9-240.9. DOI: 10.4049/jimmunol.204.supp.240.9.Peer-Reviewed Original ResearchTumor-associated macrophagesTumor microenvironmentPhenotype of tumor-associated macrophagesTumor-infiltrating immune populationsExpression of PD-L1Function of tumor-associated macrophagesExpression of scavenger receptor CD36Pro-tumor phenotypeLevels of F4/80Mouse melanoma modelMyeloid-specific deficiencyAnti-tumor functionPro-tumor functionsLipid metabolic phenotypesLipid metabolismSingle-cell RNA sequencingExpression of CD36Scavenger receptor CD36TAM subsetsPD-L1Immunosuppressive phenotypeUptake of oxLDLMacrophage lipid metabolismMelanoma modelUptake of oxidized LDL
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 exhibitTumorsHistone demethylase KDM5B is critical for PI3K‐AKT‐mTOR signaling and stemness of melanoma
Yan Q, Zhang S, Meeth K, Micevic G, Bosenberg M. Histone demethylase KDM5B is critical for PI3K‐AKT‐mTOR signaling and stemness of melanoma. The FASEB Journal 2017, 31 DOI: 10.1096/fasebj.31.1_supplement.468.1.Peer-Reviewed Original ResearchKnockdown of KDM5BHistone demethylase KDM5BMTOR signalingPI3K-AktImmune checkpoint blockadeEpigenetic stateMouse melanoma cellsCancer stem cellsMouse melanoma modelMPC populationKDM5BMelanoma formationCheckpoint blockadeTumor initiationStem cellsMelanoma modelMelanoma cellsCareer Development AwardKnockdownSignalingPilot grantsMelanoma
2016
A comprehensive system of congenic mouse melanoma models for evaluation of immune therapies
Bosenberg M, Meeth K, Damsky W. A comprehensive system of congenic mouse melanoma models for evaluation of immune therapies. The Journal Of Immunology 2016, 196: 144.19-144.19. DOI: 10.4049/jimmunol.196.supp.144.19.Peer-Reviewed Original ResearchImmune therapyMouse modelImmune systemImmune checkpoint inhibitorsSubset of patientsRenal cell carcinomaMouse melanoma modelMouse melanoma cell lineCheckpoint inhibitorsMelanoma cell linesMelanoma patientsCell carcinomaLung cancerCancer immunologyMalignant melanomaProstate cancerTherapeutic approachesMelanoma modelSkin cancerHuman melanomaTherapyTumor microenvironmentCancerFlow cytometryPatientsDNMT3b Modulates Melanoma Growth by Controlling Levels of mTORC2 Component RICTOR
Micevic G, Muthusamy V, Damsky W, Theodosakis N, Liu X, Meeth K, Wingrove E, Santhanakrishnan M, Bosenberg M. DNMT3b Modulates Melanoma Growth by Controlling Levels of mTORC2 Component RICTOR. Cell Reports 2016, 14: 2180-2192. PMID: 26923591, PMCID: PMC4785087, DOI: 10.1016/j.celrep.2016.02.010.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell Line, TumorCell ProliferationDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDown-RegulationGene Expression Regulation, NeoplasticHumansMechanistic Target of Rapamycin Complex 2Melanoma, ExperimentalMice, 129 StrainMice, Inbred C57BLMice, NudeMicroRNAsMultiprotein ComplexesNeoplasm TransplantationProportional Hazards ModelsRapamycin-Insensitive Companion of mTOR ProteinRNA InterferenceSkin NeoplasmsTOR Serine-Threonine KinasesTumor BurdenConceptsMelanoma formationPotential therapeutic targetMiR-196b expressionMouse melanoma modelPro-tumorigenic roleMTORC2 component RictorMelanoma growthTherapeutic targetMelanoma modelLoss of RictorHuman melanomaCancer typesTumor cellsMelanomaSpecific signaling pathwaysMTORC2 signalingSignaling pathwaysTurn preventsMiR-196b promoterDNA methyltransferase DNMT3BRictorControlling LevelsDNMT3BMethyltransferase DNMT3BCancer
2013
Vesicular Stomatitis Virus Variants Selectively Infect and Kill Human Melanomas but Not Normal Melanocytes
Wollmann G, Davis JN, Bosenberg MW, van den Pol AN. Vesicular Stomatitis Virus Variants Selectively Infect and Kill Human Melanomas but Not Normal Melanocytes. Journal Of Virology 2013, 87: 6644-6659. PMID: 23552414, PMCID: PMC3676084, DOI: 10.1128/jvi.03311-12.Peer-Reviewed Original ResearchConceptsVesicular stomatitis virusReplication-competent vesicular stomatitis virusMetastatic malignant melanomaRecombinant vesicular stomatitis virusMouse melanoma modelHuman melanoma samplesGene mutation statusVSV-CT9Low viral concentrationsMelanoma typesMalignant melanomaSCID miceViral oncolysisMelanoma xenograftsViral infectionMelanoma modelMutation statusMalignant transformationHuman melanomaInfectionMelanomaVirus variantsComplete protectionMelanoma samplesGene mutations
2010
A Role for ATF2 in Regulating MITF and Melanoma Development
Shah M, Bhoumik A, Goel V, Dewing A, Breitwieser W, Kluger H, Krajewski S, Krajewska M, DeHart J, Lau E, Kallenberg DM, Jeong H, Eroshkin A, Bennett DC, Chin L, Bosenberg M, Jones N, Ronai ZA. A Role for ATF2 in Regulating MITF and Melanoma Development. PLOS Genetics 2010, 6: e1001258. PMID: 21203491, PMCID: PMC3009656, DOI: 10.1371/journal.pgen.1001258.Peer-Reviewed Original ResearchConceptsMelanoma developmentMouse melanoma modelHuman melanoma cell linesMITF expressionMelanoma tissue microarrayMelanoma cell linesMetastatic diseasePoor prognosisTissue microarrayXenograft modelMelanoma modelPrimary specimensPrimary human melanocytesOncogenic BRAFMiceGene expression profilingHigh MITF expressionDependent suppressionATF2 knockdownCell linesSoft agarHuman melanocytesMelanocytesMelanoma susceptibilityPrimary melanocytes
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