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
2016
Response to Programmed Cell Death-1 Blockade in a Murine Melanoma Syngeneic Model Requires Costimulation, CD4, and CD8 T Cells
Moreno B, Zaretsky JM, Garcia-Diaz A, Tsoi J, Parisi G, Robert L, Meeth K, Ndoye A, Bosenberg M, Weeraratna AT, Graeber TG, Comin-Anduix B, Hu-Lieskovan S, Ribas A. Response to Programmed Cell Death-1 Blockade in a Murine Melanoma Syngeneic Model Requires Costimulation, CD4, and CD8 T Cells. Cancer Immunology Research 2016, 4: 845-857. PMID: 27589875, PMCID: PMC5050168, DOI: 10.1158/2326-6066.cir-16-0060.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell Line, TumorDendritic CellsInterferon-gammaLymphocytes, Tumor-InfiltratingMacrophagesMelanomaMice, Inbred C57BLMutationProgrammed Cell Death 1 ReceptorProto-Oncogene Proteins B-rafXenograft Model Antitumor AssaysConceptsPD-1 blockade therapyPD-1 blockadeCD8 T cellsBlockade therapyDendritic cellsT cellsTumor modelEffector T cell functionSyngeneic murine tumor modelsAntitumor activityPD-L1 expressionT cell primingImmune cell recruitmentT cell functionTumor-associated macrophagesMurine tumor modelsTumor-host interactionsStrong antitumor activityCD80/86 costimulationL1 therapyInflammatory profileClinical benefitMHC-IIPeripheral tissuesCell recruitmentDNMT3b 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
2015
mTORC1 Activation Blocks Braf V600E -Induced Growth Arrest but Is Insufficient for Melanoma Formation
Damsky W, Micevic G, Meeth K, Muthusamy V, Curley DP, Santhanakrishnan M, Erdelyi I, Platt JT, Huang L, Theodosakis N, Zaidi MR, Tighe S, Davies MA, Dankort D, McMahon M, Merlino G, Bardeesy N, Bosenberg M. mTORC1 Activation Blocks Braf V600E -Induced Growth Arrest but Is Insufficient for Melanoma Formation. Cancer Cell 2015, 27: 41-56. PMID: 25584893, PMCID: PMC4295062, DOI: 10.1016/j.ccell.2014.11.014.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsCell Line, TumorCell ProliferationCyclin-Dependent Kinase Inhibitor p16HumansMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MelanocytesMelanoma, ExperimentalMiceMicroRNAsMolecular Sequence DataMultiprotein ComplexesMutationNevusProtein Serine-Threonine KinasesProto-Oncogene Proteins B-rafSignal TransductionSkin NeoplasmsTOR Serine-Threonine KinasesConceptsMelanoma formationGrowth arrestStable growth arrestMTORC2/AktSTK11 lossCDKN2A lossAkt activationIGF1R signalingMice resultsActivationArrestMTORC2Nevus developmentMTORC1/2SignalingAktMelanocytic nevus developmentMelanomagenesisMTORProgressionCDKN2AMelanocytesInactivationUpregulationComplete progression
2011
β-Catenin Signaling Controls Metastasis in Braf-Activated Pten-Deficient Melanomas
Damsky WE, Curley DP, Santhanakrishnan M, Rosenbaum LE, Platt JT, Rothberg BE, Taketo MM, Dankort D, Rimm DL, McMahon M, Bosenberg M. β-Catenin Signaling Controls Metastasis in Braf-Activated Pten-Deficient Melanomas. Cancer Cell 2011, 20: 741-754. PMID: 22172720, PMCID: PMC3241928, DOI: 10.1016/j.ccr.2011.10.030.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, DifferentiationBenzamidesBeta CateninCell Transformation, NeoplasticColorectal NeoplasmsEnzyme ActivationGene Knockdown TechniquesHumansImatinib MesylateKaplan-Meier EstimateLung NeoplasmsLymphatic MetastasisMelanocytesMelanoma, ExperimentalMiceMice, 129 StrainMice, Inbred C57BLMice, TransgenicPhosphorylationPiperazinesProtein StabilityProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-aktPTEN PhosphohydrolasePyrimidinesSignal TransductionSkin NeoplasmsSplenic NeoplasmsTranscription, GeneticTumor Cells, CulturedConceptsΒ-catenin levelsPI3K/AktLymph nodesMetastatic tumorsFrequent metastasisTumor differentiationMalignant melanomaMAPK/ERKMelanoma metastasesMouse modelControl metastasisHuman melanomaMelanomaMetastasisΒ-catenin stabilizationPTEN lossCentral mediatorMetastasis regulatorsΒ-cateninSpecific changesFunctional implicationsWntLung
2009
BrafV600E cooperates with Pten loss to induce metastatic melanoma
Dankort D, Curley DP, Cartlidge RA, Nelson B, Karnezis AN, Damsky Jr W, You MJ, DePinho RA, McMahon M, Bosenberg M. BrafV600E cooperates with Pten loss to induce metastatic melanoma. Nature Genetics 2009, 41: 544-552. PMID: 19282848, PMCID: PMC2705918, DOI: 10.1038/ng.356.Peer-Reviewed Original Research
2001
Telomere dysfunction and evolution of intestinal carcinoma in mice and humans
Rudolph K, Millard M, Bosenberg M, DePinho R. Telomere dysfunction and evolution of intestinal carcinoma in mice and humans. Nature Genetics 2001, 28: 155-159. PMID: 11381263, DOI: 10.1038/88871.Peer-Reviewed Original ResearchConceptsHuman intestinal neoplasiaProgression of mouseTelomerase activationHuman colorectal carcinogenesisTelomere dysfunctionInitiated lesionsIntestinal carcinomaColorectal carcinogenesisIntestinal neoplasiaHuman colorectalDysfunctionAdvanced stageMalignant transformationTumor progressionChromosomal instabilityColon carcinomaCarcinoma transitionMacroscopic adenomasTransient telomere dysfunctionEarly carcinogenesisCancer initiationHuman cancersTelomerase activityCarcinomaDifferential effects
1993
Juxtacrine cell signaling molecules
Bosenberg M, Massagué J. Juxtacrine cell signaling molecules. Current Opinion In Cell Biology 1993, 5: 832-838. PMID: 7694603, DOI: 10.1016/0955-0674(93)90032-l.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell AdhesionCell Adhesion MoleculesCell MembraneDrosophila ProteinsEpidermal Growth FactorEye ProteinsGrowth SubstancesHematopoietic Cell Growth FactorsHumansMembrane GlycoproteinsNerve Growth FactorsReceptors, Cell SurfaceReceptors, PeptideSignal TransductionStem Cell FactorTumor Necrosis Factor-alphaConceptsCell adhesion moleculeMembrane-anchored growth factorsIntimate cell-cell contactCell-cell contactDiffusible growth factorsAdhesion moleculesGrowth factorTissue developmentIntercellular communicationJuxtacrine interactionsJuxtacrine stimulationClass of moleculesAdjacent cellsCellsRapid progressMoleculesReceptorsBiologistsMaintenanceIdentificationActivated release of membrane-anchored TGF-alpha in the absence of cytosol
Bosenberg M, Pandiella A, Massagué J. Activated release of membrane-anchored TGF-alpha in the absence of cytosol. Journal Of Cell Biology 1993, 122: 95-101. PMID: 8314849, PMCID: PMC2119606, DOI: 10.1083/jcb.122.1.95.Peer-Reviewed Original ResearchMeSH KeywordsAluminumAluminum CompoundsAnimalsCell MembraneCell Membrane PermeabilityCHO CellsCricetinaeFluoridesFluorineGTP-Binding ProteinsGuanosine 5'-O-(3-Thiotriphosphate)Guanosine DiphosphateKineticsProtein Kinase CProtein PrecursorsProtein Processing, Post-TranslationalRatsRecombinant ProteinsTetradecanoylphorbol AcetateThionucleotidesTransfectionTransforming Growth Factor alphaConceptsMembrane-anchored growth factorsHeterotrimeric G proteinsCell surfaceIndependent protein kinase CCellular proteolytic systemsStreptolysin OProtein kinase CAbsence of cytosolVesicular trafficCytoplasmic tailATP hydrolysisProteolytic componentKinase CG proteinsProteolytic systemIntact cellsPermeabilized cellsGTP gamma SBiochemical componentsCytosolAlpha cleavageTGF-alphaRegulated systemGamma SGrowth factor
1992
The cytoplasmic carboxy-terminal amino acid specifies cleavage of membrane TGFα into soluble growth factor
Bosenberg M, Pandiella A, Massagué J. The cytoplasmic carboxy-terminal amino acid specifies cleavage of membrane TGFα into soluble growth factor. Cell 1992, 71: 1157-1165. PMID: 1473151, DOI: 10.1016/s0092-8674(05)80064-9.Peer-Reviewed Original Research