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 clearanceARID1A suppresses R-loop-mediated STING-type I interferon pathway activation of anti-tumor immunity
Maxwell M, Hom-Tedla M, Yi J, Li S, Rivera S, Yu J, Burns M, McRae H, Stevenson B, Coakley K, Ho J, Gastelum K, Bell J, Jones A, Eskander R, Dykhuizen E, Shadel G, Kaech S, Hargreaves D. ARID1A suppresses R-loop-mediated STING-type I interferon pathway activation of anti-tumor immunity. Cell 2024, 187: 3390-3408.e19. PMID: 38754421, PMCID: PMC11193641, DOI: 10.1016/j.cell.2024.04.025.Peer-Reviewed Original ResearchImmune checkpoint blockadeAnti-tumor immunityIncreased CD8+ T cell infiltrationCD8+ T cell infiltrationT cell infiltrationType I IFN signalingGene expression signaturesICB treatmentCheckpoint blockadeIndependent of microsatellite instabilityARID1A mutationsCytolytic activityImmune phenotypeMurine modelCell infiltrationARID1A lossClinical trialsMutant cancersARID1AHuman cancersExpression signaturesGene upregulationMicrosatellite instabilityCancerInterferon