2023
A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better
Djureinovic D, Weiss S, Krykbaeva I, Qu R, Vathiotis I, Moutafi M, Zhang L, Perdigoto A, Wei W, Anderson G, Damsky W, Hurwitz M, Johnson B, Schoenfeld D, Mahajan A, Hsu F, Miller-Jensen K, Kluger Y, Sznol M, Kaech S, Bosenberg M, Jilaveanu L, Kluger H. A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better. Molecular Cancer 2023, 22: 182. PMID: 37964379, PMCID: PMC10644655, DOI: 10.1186/s12943-023-01884-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalHumansMelanomaMiceNivolumabReceptor Protein-Tyrosine KinasesConceptsStable diseasePartial responseMacrophage populationsThree-drug regimenUnconfirmed partial responsePhase I trialLimited treatment optionsMonocyte/macrophage populationNon-classical monocytesMurine melanoma modelTreatment-related changesResultsThirteen patientsWorse survivalI trialInflammatory tumorPatient populationTreatment optionsImmune cellsDisease progressionMurine studiesPreclinical modelsResistant melanomaAntigen presentationMurine modelCyTOF analysisSubsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma.
Horowitch B, Lee D, Ding M, Martinez-Morilla S, Aung T, Ouerghi F, Wang X, Wei W, Damsky W, Sznol M, Kluger H, Rimm D, Ishizuka J. Subsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma. Clinical Cancer Research 2023, 29: 2908-2918. PMID: 37233452, PMCID: PMC10524955, DOI: 10.1158/1078-0432.ccr-23-0215.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsHuman melanoma cell linesMelanoma cell linesPD-L1Validation cohortYale-New Haven HospitalCombination of ipilimumabPD-L1 markersImmune checkpoint blockadePD-L1 biomarkerNew Haven HospitalSTAT1 levelsCell linesWestern blot analysisCheckpoint inhibitorsCheckpoint blockadeClinical responseOverall survivalImproved survivalResistance of cancersMetastatic melanomaMelanoma responsePredict responseTreatment responseDistinct patterns
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
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