2023
New insights into programmed cell death protein 1 blockade-associated cutaneous immune-related adverse events
Micevic G, Daniels A, Flavell R. New insights into programmed cell death protein 1 blockade-associated cutaneous immune-related adverse events. British Journal Of Dermatology 2023, 189: 355-357. PMID: 37471669, PMCID: PMC10503525, DOI: 10.1093/bjd/ljad236.Peer-Reviewed Original ResearchConceptsCutaneous immune-related adverse eventsImmune-related adverse eventsSelf-reactive T cellsCheckpoint receptor PD-1PD-1 inhibitorsHalf of patientsImmune checkpoint blockadeAntitumor immune responseReceptor PD-1Adverse eventsCheckpoint blockadePD-1Immune toleranceCTLA-4T cellsImmune responseLandmark studiesMolecular mechanismsFunctional roleCritical functional rolePatientsBlockadeDermatologistsImportant cluesIL-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
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
Targeting the neonatal Fc receptor in pemphigus: safety first
Micevic G, Lo SN, Rajan N. Targeting the neonatal Fc receptor in pemphigus: safety first. British Journal Of Dermatology 2021, 186: 389-390. PMID: 34961930, PMCID: PMC9295899, DOI: 10.1111/bjd.20939.Peer-Reviewed Original ResearchKDM5B 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
RAP80 and BRCA1 PARsylation protect chromosome integrity by preventing retention of BRCA1-B/C complexes in DNA repair foci
Vohhodina J, Toomire KJ, Petit SA, Micevic G, Kumari G, Botchkarev VV, Li Z, Livingston DM, Hu Y. RAP80 and BRCA1 PARsylation protect chromosome integrity by preventing retention of BRCA1-B/C complexes in DNA repair foci. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 2084-2091. PMID: 31932421, PMCID: PMC6995001, DOI: 10.1073/pnas.1908003117.Peer-Reviewed Original ResearchConceptsHomologous recombination-mediated repairNuclear fociRecombination-mediated repairDNA repair fociPoly ADP-ribosylationProtein RAP80Chromatin structureChromosome integrityBRCA1 complexGenome disordersRepair fociRAP80Intracellular developmentPresence of BRCA1C complexActivity promotesSimultaneous lossBRCA1Complex formationNormal interactionComplexesPARsylationDNARibosylationChromosomal disorders
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 applicationsExpressionPatientsInhibition 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
p90RSK Blockade Inhibits Dual BRAF and MEK Inhibitor-Resistant Melanoma by Targeting Protein Synthesis
Theodosakis N, Micevic G, Langdon CG, Ventura A, Means R, Stern DF, Bosenberg MW. p90RSK Blockade Inhibits Dual BRAF and MEK Inhibitor-Resistant Melanoma by Targeting Protein Synthesis. Journal Of Investigative Dermatology 2017, 137: 2187-2196. PMID: 28599981, PMCID: PMC6342201, DOI: 10.1016/j.jid.2016.12.033.Peer-Reviewed Original ResearchConceptsProtein synthesisRibosomal S6 kinase (RSK) familyPatient-derived melanoma cell linesDifferential protein expressionReverse phase protein arrayPhase protein arrayTranslation complexesKinase familyBI-D1870RSK inhibitorsMelanoma cell linesProtein arraysCell proliferationInhibitor treatmentProtein expressionCell linesNew targetsHuman melanoma patientsBRAF inhibitor vemurafenibAberrant DNA methylation in melanoma: biomarker and therapeutic opportunities
Micevic G, Theodosakis N, Bosenberg M. Aberrant DNA methylation in melanoma: biomarker and therapeutic opportunities. Clinical Epigenetics 2017, 9: 34. PMID: 28396701, PMCID: PMC5381063, DOI: 10.1186/s13148-017-0332-8.Peer-Reviewed Original ResearchConceptsAberrant DNA methylationDNA methylationMethylation changesDNA methylation changesEpigenetic hallmarkMelanoma formationMethylation signaturesMethylationImportant unresolved questionsBiomarker opportunitiesTherapeutic opportunitiesTherapeutic developmentMethylation methodUnresolved questionsTherapeutic potentialImportant roleRecent advancesPotential biomarkersGenesRecent developmentsHallmarkConsiderable effortDevelopmentBiomarkersAdvancesAttenuation of genome-wide 5-methylcytosine level is an epigenetic feature of cutaneous malignant melanomas
Micevic G, Theodosakis N, Taube JM, Bosenberg MW, Rodi N. Attenuation of genome-wide 5-methylcytosine level is an epigenetic feature of cutaneous malignant melanomas. Melanoma Research 2017, 27: 85-96. PMID: 27997431, PMCID: PMC5812886, DOI: 10.1097/cmr.0000000000000315.Peer-Reviewed Original ResearchConceptsS-adenosyl methionineMelanoma cell linesEpigenetic featuresCell linesInactive chromatin regionsGenome-wide increaseUniversal methyl group donorMethyl group donorChromatin regionsCancer epigenomeEpigenetic modificationsEpigenetic abnormalitiesCytosine residuesMelanoma cell growthEpigenome modulationMalignant melanomaCell growthCovalent changesGroup donorSubcytotoxic levelsChemical substratesMelanoma cellsCutaneous malignant melanomaDose-dependent increaseResidues
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 biologyImmunologyTherapyCancerMiceStereotactic Ablative Radiation Therapy Combined With Immunotherapy for Solid Tumors
Brooks ED, Schoenhals JE, Tang C, Micevic G, Gomez DR, Chang JY, Welsh JW. Stereotactic Ablative Radiation Therapy Combined With Immunotherapy for Solid Tumors. The Cancer Journal 2016, 22: 257-266. PMID: 27441745, PMCID: PMC5812885, DOI: 10.1097/ppo.0000000000000210.Peer-Reviewed Original ResearchConceptsStereotactic ablative radiation therapyImmune checkpoint therapyAblative radiation therapyRadiation therapyNovel therapeuticsImmune checkpoint inhibitionImmune checkpoint inhibitorsLocal treatment optionsEncouraging clinical responsesClinical responseExperience relapseSystemic therapyTreatment optionsClinical studiesLocal irradiationSystemic effectsImmunogenic effectsImmunotherapySolid tumorsTherapyNumerous cancersTumorsTherapeuticsRelapsePatientsGenome-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 ResearchIntegrative discovery of CD98 as a melanoma biomarker
Theodosakis N, Micevic G, Sharma R, Baras AS, Lazova R, Bosenberg MW, Rodić N. Integrative discovery of CD98 as a melanoma biomarker. Pigment Cell & Melanoma Research 2016, 29: 385-387. PMID: 26850337, DOI: 10.1111/pcmr.12464.Peer-Reviewed Original ResearchMultilevel Genomics-Based Taxonomy of Renal Cell Carcinoma
Chen F, Zhang Y, Şenbabaoğlu Y, Ciriello G, Yang L, Reznik E, Shuch B, Micevic G, De Velasco G, Shinbrot E, Noble MS, Lu Y, Covington KR, Xi L, Drummond JA, Muzny D, Kang H, Lee J, Tamboli P, Reuter V, Shelley CS, Kaipparettu BA, Bottaro DP, Godwin AK, Gibbs RA, Getz G, Kucherlapati R, Park PJ, Sander C, Henske EP, Zhou JH, Kwiatkowski DJ, Ho TH, Choueiri TK, Hsieh JJ, Akbani R, Mills GB, Hakimi AA, Wheeler DA, Creighton CJ. Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma. Cell Reports 2016, 14: 2476-2489. PMID: 26947078, PMCID: PMC4794376, DOI: 10.1016/j.celrep.2016.02.024.Peer-Reviewed Original ResearchMeSH KeywordsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCarcinoma, Renal CellChromatinGene Expression ProfilingGenomicsHumansKidney NeoplasmsMicroRNAsMutationPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRNA, MessengerSignal TransductionSurvival RateTOR Serine-Threonine KinasesConceptsRenal cell carcinomaMajor genomic subtypesChromatin modifier genesComprehensive molecular characterizationGenomic subtypesAggressive clear cell renal cell carcinomaCell carcinomaGene fusionsModifier genesMolecular characterizationMolecular signaturesClear cell renal cell carcinomaCell renal cell carcinomaSpecific pathwaysPapillary renal cell carcinomaImmune checkpoint markersT-cell infiltratesMolecular changesTFE3 gene fusionsSite of originCell infiltrateCheckpoint markersHistologic typePatient survivalDisease subsetsDNMT3b 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
BRAF Inhibition Decreases Cellular Glucose Uptake in Melanoma in Association with Reduction in Cell Volume
Theodosakis N, Held MA, Marzuka-Alcala A, Meeth KM, Micevic G, Long GV, Scolyer RA, Stern DF, Bosenberg MW. BRAF Inhibition Decreases Cellular Glucose Uptake in Melanoma in Association with Reduction in Cell Volume. Molecular Cancer Therapeutics 2015, 14: 1680-1692. PMID: 25948295, PMCID: PMC4497841, DOI: 10.1158/1535-7163.mct-15-0080.Peer-Reviewed Original ResearchConceptsGlucose uptakeWeeks of treatmentBRAF kinase inhibitorsHigh response rateTumor cell deathMetastatic diseaseTransmembrane glucose transportMetastatic melanomaPatient cohortCellular glucose uptakeRadiographic changesVemurafenib treatmentBRAF inhibitorsBRAF inhibitionResponse rateEmission tomographyPhysiologic parametersNew protein translationKinase inhibitorsEarly responseImportant physiologic parametersCell volumeMelanomaVolume reductionCell volume regulationmTORC1 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