2022
The Crossroads of Cancer Epigenetics and Immune Checkpoint Therapy.
Micevic G, Bosenberg M, Yan Q. The Crossroads of Cancer Epigenetics and Immune Checkpoint Therapy. Clinical Cancer Research 2022, 29: 1173-1182. PMID: 36449280, PMCID: PMC10073242, DOI: 10.1158/1078-0432.ccr-22-0784.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmune checkpoint inhibitorsImmune checkpoint therapyT cell exhaustionCheckpoint therapyAntitumor immune responseT cell populationsCell-intrinsic immunityTypes of cancerViral mimicry responseLow response rateCheckpoint inhibitorsCurrent immunotherapiesPancreatic cancerSustained responsePreclinical modelsTreatment outcomesImmune responseEndogenous antigensResponse rateTumor typesMultiple epigenetic regulatorsCritical mediatorLow immunogenicityTherapyCancer
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
2024
Setdb1-loss induces type-I interferons and immune clearance of melanoma.
McGeary M, Damsky W, Daniels A, Lang S, Xu Q, Song E, Huet-Calderwood C, Lou H, Paradkar S, Micevic G, Kaech S, Calderwood D, Turk B, Yan Q, Iwasaki A, Bosenberg M. Setdb1-loss induces type-I interferons and immune clearance of melanoma. Cancer Immunology Research 2024 PMID: 39589394, DOI: 10.1158/2326-6066.cir-23-0514.Peer-Reviewed Original ResearchT cell infiltrationMHC-I expressionType I interferonImmune clearanceCD8+ T cell-dependent mannerIncreased CD8+ T cell infiltrationCD8+ T cell infiltrationDecreased MHC-I expressionAnti-cancer immune responseT cell-dependent mannerCD8+ T cellsDecreased T-cell infiltrationComplete tumor clearanceImmunity to melanomaIncreased melanoma growthInflamed tumor microenvironmentLoss of SETDB1Type I interferon receptorTreatment of melanomaType I interferon signalingWhole-genome CRISPR screenEndogenous retrovirusesType I interferon expressionMetastatic diseaseTumor clearance
2023
1025 Tumor-specific CD8+ T cells epigenetically licensed by IL-7R are critical for anti-tumor immunity in melanoma
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. 1025 Tumor-specific CD8+ T cells epigenetically licensed by IL-7R are critical for anti-tumor immunity in melanoma. 2023, a1133-a1133. DOI: 10.1136/jitc-2023-sitc2023.1025.Peer-Reviewed Original ResearchIL-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
2020
668 Ulcerated melanomas exhibit epigenetic changes in epidermal and immune response genes
Micevic G, Bosenberg M. 668 Ulcerated melanomas exhibit epigenetic changes in epidermal and immune response genes. Journal Of Investigative Dermatology 2020, 140: s90. DOI: 10.1016/j.jid.2020.03.680.Peer-Reviewed Original Research
2018
PD‐L1 methylation regulates PD‐L1 expression and is associated with melanoma survival
Micevic G, Thakral D, McGeary M, Bosenberg M. PD‐L1 methylation regulates PD‐L1 expression and is associated with melanoma survival. Pigment Cell & Melanoma Research 2018, 32: 435-440. PMID: 30343532, PMCID: PMC6475614, DOI: 10.1111/pcmr.12745.Peer-Reviewed Original ResearchConceptsPD-L1 expressionDNA methylationPD-1/PD-L1 immune checkpointIndependent survival prognostic factorPD-L1 promoter methylationPD-L1 immune checkpointSurvival prognostic factorsPD-L1 promoterPromoter DNA methylationOverall survivalImmune checkpointsPrognostic factorsMelanoma patientsMelanoma survivalEpigenetic mechanismsTranscriptional phenotypeClinical importanceMelanomaCpG lociMethylationPromoter methylationSurvivalTherapeutic applicationsExpressionPatients1185 DNA hypermethylation of MHC class-I genes is associated with reduced expression and survival in melanoma
Micevic G, Thakral D, McGeary M, Bosenberg M. 1185 DNA hypermethylation of MHC class-I genes is associated with reduced expression and survival in melanoma. Journal Of Investigative Dermatology 2018, 138: s201. DOI: 10.1016/j.jid.2018.03.1200.Peer-Reviewed Original Research
2017
(S029) Development of an Immune-Associated Molecular Signature Predicting Melanoma Survival
Micevic G, Muthusamy V, Pupo G, Scolyer R, Long G, Bosenberg M. (S029) Development of an Immune-Associated Molecular Signature Predicting Melanoma Survival. International Journal Of Radiation Oncology • Biology • Physics 2017, 98: e9. DOI: 10.1016/j.ijrobp.2017.02.065.Peer-Reviewed Original Research789 Inhibition of isoprenylation synergizes with MAPK blockade to prevent growth in treatment-resistant melanoma
Theodosakis N, Langdon C, Micevic G, Stern D, Bosenberg M. 789 Inhibition of isoprenylation synergizes with MAPK blockade to prevent growth in treatment-resistant melanoma. Journal Of Investigative Dermatology 2017, 137: s136. DOI: 10.1016/j.jid.2017.02.814.Peer-Reviewed Original Research791 DNA methyltransferases play important but antagonistic roles in melanoma formation and growth
Micevic G, Bosenberg M. 791 DNA methyltransferases play important but antagonistic roles in melanoma formation and growth. Journal Of Investigative Dermatology 2017, 137: s136. DOI: 10.1016/j.jid.2017.02.816.Peer-Reviewed Original Research
2016
637 miRNA processing enzyme regulates melanoma formation and growth
Micevic G, Meeth K, Theodosakis N, Ventura A, Liu X, Bosenberg M. 637 miRNA processing enzyme regulates melanoma formation and growth. Journal Of Investigative Dermatology 2016, 136: s113. DOI: 10.1016/j.jid.2016.02.678.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
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