2023
Manipulating mitochondrial electron flow enhances tumor immunogenicity
Mangalhara K, Varanasi S, Johnson M, Burns M, Rojas G, Esparza Moltó P, Sainz A, Tadepalle N, Abbott K, Mendiratta G, Chen D, Farsakoglu Y, Kunchok T, Hoffmann F, Parisi B, Rincon M, Vander Heiden M, Bosenberg M, Hargreaves D, Kaech S, Shadel G. Manipulating mitochondrial electron flow enhances tumor immunogenicity. Science 2023, 381: 1316-1323. PMID: 37733872, PMCID: PMC11034774, DOI: 10.1126/science.abq1053.Peer-Reviewed Original ResearchConceptsElectron transport chainMethylation-controlled J proteinMitochondrial electron transport chainElectron flowMitochondrial electron flowJ-proteinsEpigenetic activationTransport chainMitochondrial respirationTumor growthPresentation genesElectron entryNoncancer cellsMelanoma tumor growthCommon mechanismTherapeutic potentialGenesRelative contributionProteinGrowthKnockoutAntigen presentationRespirationT cell-mediated killingExpressionDiscovery of decreased ferroptosis in male colorectal cancer patients with KRAS mutations
Yan H, Talty R, Jain A, Cai Y, Zheng J, Shen X, Muca E, Paty P, Bosenberg M, Khan S, Johnson C. Discovery of decreased ferroptosis in male colorectal cancer patients with KRAS mutations. Redox Biology 2023, 62: 102699. PMID: 37086630, PMCID: PMC10172914, DOI: 10.1016/j.redox.2023.102699.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorColorectal NeoplasmsFemaleFerroptosisHumansMaleMetabolomicsPrognosisProto-Oncogene Proteins p21(ras)Sex FactorsConceptsKRAS mutant tumorsMale CRC patientsCRC patientsMale patientsKRAS mutationsMutant tumorsOverall survivalMale colorectal cancer patientsKRAS wild-type tumorsAberrant tumor metabolismColorectal cancer patientsCRC patient cohortsColorectal cancer casesFerroptosis-related genesWild-type tumorsNovel potential avenuesNormal colon tissuesPoor OSKRAS statusAdverse outcomesCRC cellsPatient cohortCancer patientsType tumorsCancer cases
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
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
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