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
Developing synthetic tools to decipher the tumor–immune interactome
Weizman O, Luyten S, Lu P, Song E, Qin K, Mostaghimi D, Ring A, Iwasaki A. Developing synthetic tools to decipher the tumor–immune interactome. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2306632120. PMID: 37871202, PMCID: PMC10622925, DOI: 10.1073/pnas.2306632120.Peer-Reviewed Original ResearchConceptsImmune cellsImmune-based therapiesTumor-immune cell interactionsDifferent immunotherapiesRetroviral reportersSensitive tumorsImmune surveillanceTumor subtypesTumor microenvironmentSynthetic Notch receptorCell interactionsCell contactTissue functionTissue locationNotch receptorsVivoOptimal tissue functionCellsComprehensive landscapeImmunotherapyTherapyTumorsImmunogenicitySubtypesType 2 Dendritic Cells Orchestrate a Local Immune Circuit to Confer Antimetastatic Immunity
Weizman O, Luyten S, Krykbaeva I, Song E, Mao T, Bosenberg M, Iwasaki A. Type 2 Dendritic Cells Orchestrate a Local Immune Circuit to Confer Antimetastatic Immunity. The Journal Of Immunology 2023, 210: 1146-1155. PMID: 36881866, PMCID: PMC10067787, DOI: 10.4049/jimmunol.2200697.Peer-Reviewed Original ResearchConceptsType 2 dendritic cellsMetastatic burdenImmune circuitsDendritic cellsConventional type 2 dendritic cellsSyngeneic murine melanomaNK cell compartmentImmune cell responsesColon cancer modelEarly metastatic seedingMetastatic controlTranscription factor IRF3DC populationsNK cellsProinflammatory cytokinesNucleic acid sensingPrimary tumorEffector responsesMetastatic spreadDisease outcomeIntracardiac injectionT cellsInitial immunityTissue-specific ablationCancer modelResponse to: Elevated L1 expression in ataxia telangiectasia likely explained by an RNA-seq batch effect
Takahashi T, Stoiljkovic M, Song E, Gao X, Yasumoto Y, Kudo E, Carvalho F, Kong Y, Park A, Shanabrough M, Szigeti-Buck K, Liu Z, Kristant A, Zhang Y, Sulkowski P, Glazer P, Kaczmarek L, Horvath T, Iwasaki A. Response to: Elevated L1 expression in ataxia telangiectasia likely explained by an RNA-seq batch effect. Neuron 2023, 111: 612-613. PMID: 36863323, DOI: 10.1016/j.neuron.2023.02.006.Peer-Reviewed Original Research
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