2024
Causes of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era
Lee D, McNamara M, Yang A, Yaskolko M, Kluger H, Tran T, Olino K, Clune J, Sznol M, Ishizuka J. Causes of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era. Pigment Cell & Melanoma Research 2024, 37: 847-853. PMID: 39073002, DOI: 10.1111/pcmr.13188.Peer-Reviewed Original ResearchSite of metastasisPattern of metastatic diseaseMelanoma mortalityRetrospective observational cohort studyCause of cancer mortalityDistant lymph nodesObservational cohort studyDiagnosis to deathImmunotherapy eraAdvanced melanomaMetastatic diagnosisMetastatic diseaseMetastatic melanomaImmunotherapy treatmentRespiratory failureCause of deathMedian timeLymph nodesTherapeutic advancesCohort studyMelanomaImmunotherapyMechanism of deathPatientsEnd of lifeSpatially Informed Gene Signatures for Response to Immunotherapy in Melanoma.
Aung T, Warrell J, Martinez-Morilla S, Gavrielatou N, Vathiotis I, Yaghoobi V, Kluger H, Gerstein M, Rimm D. Spatially Informed Gene Signatures for Response to Immunotherapy in Melanoma. Clinical Cancer Research 2024, 30: 3520-3532. PMID: 38837895, PMCID: PMC11326985, DOI: 10.1158/1078-0432.ccr-23-3932.Peer-Reviewed Original ResearchGene signatureResistance to immunotherapyResponse to immunotherapyPrediction of treatment outcomeResistant to treatmentAccurate prediction of treatment outcomePredictive of responseImmunotherapy outcomesMelanoma patientsMelanoma specimensValidation cohortPatient stratificationDiscovery cohortTreatment outcomesImmunotherapyMelanomaTumorPatientsCohortS100BOutcomesGene expression dataGenesCD68+macrophagesExpression data
2023
Society for Immunotherapy of Cancer (SITC) checkpoint inhibitor resistance definitions: efforts to harmonize terminology and accelerate immuno-oncology drug development
Tawbi H, Sullivan R, Feltquate D, LaVallee T, Rizvi N, Sharon E, Sosman J, Kluger H. Society for Immunotherapy of Cancer (SITC) checkpoint inhibitor resistance definitions: efforts to harmonize terminology and accelerate immuno-oncology drug development. Journal For ImmunoTherapy Of Cancer 2023, 11: e007309. PMID: 37487665, PMCID: PMC10373737, DOI: 10.1136/jitc-2023-007309.Peer-Reviewed Original ResearchImmune Resistance Mechanisms and the Road to Personalized Immunotherapy.
Piper M, Kluger H, Ruppin E, Hu-Lieskovan S. Immune Resistance Mechanisms and the Road to Personalized Immunotherapy. American Society Of Clinical Oncology Educational Book 2023, 43: e390290. PMID: 37459578, DOI: 10.1200/edbk_390290.Peer-Reviewed Original ResearchSociety for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors
Kluger H, Barrett J, Gainor J, Hamid O, Hurwitz M, LaVallee T, Moss R, Zappasodi R, Sullivan R, Tawbi H, Sharon E. Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors. Journal For ImmunoTherapy Of Cancer 2023, 11: e005921. PMID: 36918224, PMCID: PMC10016305, DOI: 10.1136/jitc-2022-005921.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsCheckpoint inhibitorsAnti-PD-1 immune checkpoint inhibitorTrial designConsensus definitionConsensus clinical definitionExtended disease controlNew combination regimensImmunotherapy of cancerStandard of careLong-term survivalClinical trial designICI combinationsInitial immunotherapyMetastatic settingTreatment discontinuationDurable responsesTreatment landscapeCombination regimensMechanisms of resistancePerioperative settingPrimary resistanceClinical definitionDefinition of resistanceImmunotherapySociety for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors with targeted therapies
Atkins M, Ascierto P, Feltquate D, Gulley J, Johnson D, Khushalani N, Sosman J, Yap T, Kluger H, Sullivan R, Tawbi H. Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors with targeted therapies. Journal For ImmunoTherapy Of Cancer 2023, 11: e005923. PMID: 36918225, PMCID: PMC10016252, DOI: 10.1136/jitc-2022-005923.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsConsensus definitionCheckpoint inhibitorsAntiangiogenic therapySingle-agent immune checkpoint inhibitorsConsensus clinical definitionSolid tumor settingTumor immune microenvironmentImmunotherapy of cancerDurable disease controlClinical trial designSignal transduction inhibitorsICI combinationsEndometrial cancerImproved survivalRandomized trialsImmune microenvironmentMechanisms of resistanceHepatocellular carcinomaClinical definitionKidney cancerImmunotherapyTumor settingsCombination treatmentTrial design
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 therapyBlockadeCirculating clonally expanded T cells reflect functions of tumor-infiltrating T cells
Lucca LE, Axisa PP, Lu B, Harnett B, Jessel S, Zhang L, Raddassi K, Zhang L, Olino K, Clune J, Singer M, Kluger HM, Hafler DA. Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells. Journal Of Experimental Medicine 2021, 218: e20200921. PMID: 33651881, PMCID: PMC7933991, DOI: 10.1084/jem.20200921.Peer-Reviewed Original ResearchConceptsTumor-infiltrating T cellsT cellsUnique transcriptional patternsFeatures of exhaustionLongitudinal immune monitoringPeripheral immune environmentsT cell responsesT cell functionSingle-cell levelTranscriptional patternsTCR sharingTerminal exhaustionImmune environmentImmune monitoringCancer immunotherapyMetastatic melanomaEffector functionsCell responsesTumor tissueGene signatureTumorsCell functionImmunotherapyTCRαβBlood
2018
Inflammatory eruptions associated with immune checkpoint inhibitor therapy: A single-institution retrospective analysis with stratification of reactions by toxicity and implications for management
Coleman E, Ko C, Dai F, Tomayko MM, Kluger H, Leventhal JS. Inflammatory eruptions associated with immune checkpoint inhibitor therapy: A single-institution retrospective analysis with stratification of reactions by toxicity and implications for management. Journal Of The American Academy Of Dermatology 2018, 80: 990-997. PMID: 30399387, PMCID: PMC6420863, DOI: 10.1016/j.jaad.2018.10.062.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsDrug EruptionsExanthemaFemaleHumansIpilimumabLichenoid EruptionsMaleMiddle AgedNivolumabRetrospective StudiesSkin NeoplasmsStevens-Johnson SyndromeWithholding TreatmentConceptsInflammatory eruptionsCheckpoint inhibitorsTherapeutic responseImmune checkpoint inhibitor therapySingle tertiary care centerSingle-institution retrospective analysisYale-New Haven HospitalCheckpoint inhibitor therapyTertiary care centerMinority of patientsInpatient dermatology serviceDegree of severityMost rashesInhibitor therapyRetrospective studyTopical treatmentEarly recognitionMedical recordsCare centerInflammatory reactionRetrospective analysisDermatology servicesImmunotherapyMean latencyGrade 2
2016
Possible Interaction of Anti–PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases
Alomari AK, Cohen J, Vortmeyer AO, Chiang A, Gettinger S, Goldberg S, Kluger HM, Chiang VL. Possible Interaction of Anti–PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases. Cancer Immunology Research 2016, 4: 481-487. PMID: 26994250, DOI: 10.1158/2326-6066.cir-15-0238.Peer-Reviewed Original ResearchConceptsStereotactic radiosurgeryBrain metastasesInitiation of immunotherapyPD-1 mAbImmune-modulating therapyModalities of treatmentRadiologic progressionSurgical resectionSystemic therapyDeath-1Radiologic findingsMetastatic malignancyReactive astrocytosisPathologic examinationTreatment regimensHistopathologic examinationWall infiltrationT lymphocytesPatientsTumor progressionMonoclonal antibodiesBiologic interactionsRadiation-induced changesImmunotherapyMalignancy
2015
Does immunotherapy increase the rate of radiation necrosis after radiosurgical treatment of brain metastases?
Colaco RJ, Martin P, Kluger HM, Yu JB, Chiang VL. Does immunotherapy increase the rate of radiation necrosis after radiosurgical treatment of brain metastases? Journal Of Neurosurgery 2015, 125: 17-23. PMID: 26544782, DOI: 10.3171/2015.6.jns142763.Peer-Reviewed Original ResearchConceptsTreatment-related imaging changesCytotoxic chemotherapyRadiation necrosisBrain metastasesSystemic therapyStereotactic Gamma Knife radiosurgeryMedian overall survivalGamma knife radiosurgeryHigh-dose radiationChemotherapy eraGK surgeryImmunotherapy increasesMedian followConclusions PatientsOverall survivalImaging changesGK treatmentKnife radiosurgeryInflammatory reactionStereotactic radiosurgeryLower riskRadiosurgical treatmentPatientsImmunotherapyTherapy
2012
Immunotherapy for metastatic melanoma
Zito CR, Kluger HM. Immunotherapy for metastatic melanoma. Journal Of Cellular Biochemistry 2012, 113: 725-734. PMID: 22006439, DOI: 10.1002/jcb.23402.Peer-Reviewed Original ResearchConceptsMetastatic melanomaPromising investigational approachesTreatment of melanomaImmunogenic tumorsAntitumor immunityCTLA-4Interleukin-2First cytokineInvestigational approachesProlonged responseMelanomaMonoclonal antibodiesImmunotherapyTreatmentIpilimumabPatientsCytokinesTumorsSmall subsetDiseaseImmunityAntibodies
2010
Ipilimumab: a promising immunotherapy for melanoma.
Thumar JR, Kluger HM. Ipilimumab: a promising immunotherapy for melanoma. Oncology 2010, 24: 1280-8. PMID: 21294471.Peer-Reviewed Original ResearchConceptsMetastatic melanomaClinical trialsCytotoxic T-lymphocyte antigen-4Recent phase III trialsT-lymphocyte antigen-4Overall survival benefitPhase III trialsDrug-related toxicityAntibody-based targetingIII trialsSurvival benefitPromising immunotherapyAntigen-4Immune modulationTreatment responseTherapeutic benefitMelanomaIpilimumabTrialsImmunotherapyUnique challengesCancerClinicians