2023
IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2304319120. PMID: 37459511, PMCID: PMC10372654, DOI: 10.1073/pnas.2304319120.Peer-Reviewed Original ResearchConceptsIL-7R expressionT cellsIL-7RAntitumor memorySuperior antitumor efficacyCell-based therapiesTumor-specific T cellsAntigen-specific T cellsAntitumor efficacyPowerful antitumor immune responseMarkers of exhaustionTumor-specific CD8Antitumor immune responseIndependent prognostic factorAntitumor immune memoryMemory T cellsMajor risk factorSuperior antitumor activityFunctional CD8Memory CD8Prognostic factorsSurgical resectionAdvanced melanomaLymph nodesNaive mice
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
2018
Inhibition of isoprenylation synergizes with MAPK blockade to prevent growth in treatment‐resistant melanoma, colorectal, and lung cancer
Theodosakis N, Langdon CG, Micevic G, Krykbaeva I, Means RE, Stern DF, Bosenberg MW. Inhibition of isoprenylation synergizes with MAPK blockade to prevent growth in treatment‐resistant melanoma, colorectal, and lung cancer. Pigment Cell & Melanoma Research 2018, 32: 292-302. PMID: 30281931, PMCID: PMC6590911, DOI: 10.1111/pcmr.12742.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell ProliferationColorectal NeoplasmsDrug Resistance, NeoplasmDrug SynergismHumansHydroxymethylglutaryl-CoA Reductase InhibitorsLung NeoplasmsMaleMelanomaMevalonic AcidMice, NudeMitogen-Activated Protein KinasesPrenylationProtein Kinase InhibitorsProtein Processing, Post-TranslationalSignal TransductionConceptsUseful adjunctive therapyHMG-CoA reductase inhibitorsAnti-tumor effectsAdjunctive therapyInhibition of isoprenylationLung cancerMEK inhibitionReductase inhibitorsMAPK blockadeDriver mutationsAdditional studiesStatinsTherapyMelanomaTumorsVemurafenibMAPK pathwayDownstream metabolitesInhibitionMAPKAdjunctiveColorectalSelumetinibBlockadeCancer
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
2016
The YUMM lines: a series of congenic mouse melanoma cell lines with defined genetic alterations
Meeth K, Wang JX, Micevic G, Damsky W, Bosenberg MW. The YUMM lines: a series of congenic mouse melanoma cell lines with defined genetic alterations. Pigment Cell & Melanoma Research 2016, 29: 590-597. PMID: 27287723, PMCID: PMC5331933, DOI: 10.1111/pcmr.12498.Peer-Reviewed Original ResearchConceptsMouse melanoma cell lineMelanoma cell linesCell linesMouse cancer cell linesVariety of cancersCancer cell linesMouse melanoma linesImmune therapyTumor immunologyCancer immunologyHost miceMouse modelCancer modelMelanoma linesDriver mutationsGenetic alterationsCancer biologyImmunologyTherapyCancerMiceGenome-wide characterization of human L1 antisense promoter-driven transcripts
Criscione SW, Theodosakis N, Micevic G, Cornish TC, Burns KH, Neretti N, Rodić N. Genome-wide characterization of human L1 antisense promoter-driven transcripts. BMC Genomics 2016, 17: 463. PMID: 27301971, PMCID: PMC4908685, DOI: 10.1186/s12864-016-2800-5.Peer-Reviewed Original ResearchConceptsL1 antisense promoterAntisense promoterChimeric transcriptsHuman genomeGenome-wide characterizationGene transcriptional start siteHuman-specific subfamilyTranscriptional start siteYY1 transcription factorRNA-seq dataGenic transcriptsAntisense promoter activitySense promoterCellular transcriptomeMultiple cell linesHistone modificationsL1 biologyNeighboring genesTransposable elementsGenBank ESTsAntisense transcriptsHuman genesTranscription factorsStart siteActive promotersCell and Tissue Display
Theodosakis N, Micevic G, Bosenberg MW, Rodić N. Cell and Tissue Display. Journal Of Histochemistry & Cytochemistry 2016, 64: 403-411. PMID: 27270967, PMCID: PMC4931762, DOI: 10.1369/0022155416651065.Peer-Reviewed Original ResearchDNMT3b 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
Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses
Ho PC, Bihuniak JD, Macintyre AN, Staron M, Liu X, Amezquita R, Tsui YC, Cui G, Micevic G, Perales JC, Kleinstein SH, Abel ED, Insogna KL, Feske S, Locasale JW, Bosenberg MW, Rathmell JC, Kaech SM. Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses. Cell 2015, 162: 1217-1228. PMID: 26321681, PMCID: PMC4567953, DOI: 10.1016/j.cell.2015.08.012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCD4-Positive T-LymphocytesEndoplasmic ReticulumGlycolysisHexokinaseImmunotherapyLymphocytes, Tumor-InfiltratingMelanomaMiceMonitoring, ImmunologicNFATC Transcription FactorsPhosphoenolpyruvateReceptors, Antigen, T-CellSarcoplasmic Reticulum Calcium-Transporting ATPasesSignal TransductionTransforming Growth Factor betaTumor MicroenvironmentConceptsAnti-tumor T cell responsesT cell responsesT cellsEffector functionsCell responsesTumor-reactive T cellsTumor-infiltrating T cellsPhosphoenolpyruvate carboxykinase 1Tumoricidal effector functionsTumor-specific CD4CD8 T cellsT cell activityMelanoma-bearing miceAerobic glycolysisActivated T cellsMetabolic checkpointTumor growthCell activityTumor microenvironmentNFAT SignalingMetabolic reprogrammingCarboxykinase 1Anabolic metabolismCellsATPase activitymTORC1 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
2014
Mitochondrial function in melanoma
Theodosakis N, Micevic G, Kelly DP, Bosenberg M. Mitochondrial function in melanoma. Archives Of Biochemistry And Biophysics 2014, 563: 56-59. PMID: 24997363, DOI: 10.1016/j.abb.2014.06.028.Peer-Reviewed Original Research