2023
Subsets 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 patternsSociety 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
Clinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells
Tran TT, Rane CK, Zito CR, Weiss SA, Jessel S, Lucca L, Lu BY, Oria VO, Adeniran A, Chiang VL, Omay SB, Hafler DA, Kluger HM, Jilaveanu LB. Clinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells. Cancers 2021, 13: 1049. PMID: 33801444, PMCID: PMC7958624, DOI: 10.3390/cancers13051049.Peer-Reviewed Original ResearchPDCD4 expressionImproved survivalTumor-Associated Immune CellsTumor microenvironmentNeoplastic progressionBrain metastasis outcomesExtracranial metastatic diseaseMelanoma brain metastasesNatural killer cellsBrain metastasis samplesImmune cell infiltrationImmune cell subsetsMultiple tissue microarraysExpression of PDCD4Brain metastasesMetastatic diseaseClinical outcomesKiller cellsClinicopathological variablesIntracranial metastasesCell subsetsCell infiltrationCell death 4Immune cellsPrimary melanoma
2016
The Treatment of Melanoma Brain Metastases
Kibbi N, Kluger H. The Treatment of Melanoma Brain Metastases. Current Oncology Reports 2016, 18: 73. PMID: 27822695, DOI: 10.1007/s11912-016-0555-4.Peer-Reviewed Original ResearchConceptsMelanoma brain metastasesBrain metastasesSystemic therapyClinical trialsAsymptomatic brain metastasesPrognosis of patientsUntreated brain metastasesPopulation of patientsOngoing clinical trialsCentral nervous systemMBM patientsCerebral edemaTreatment landscapeImproved survivalIntracranial metastasesMetastatic melanomaStereotactic radiosurgeryNew therapiesLocal modalitiesNervous systemPatientsDrug AdministrationRegistration trialsMetastasisEarly intervention
2015
Characterization of PD-L1 Expression and Associated T-cell Infiltrates in Metastatic Melanoma Samples from Variable Anatomic Sites
Kluger HM, Zito CR, Barr ML, Baine MK, Chiang VL, Sznol M, Rimm DL, Chen L, Jilaveanu LB. Characterization of PD-L1 Expression and Associated T-cell Infiltrates in Metastatic Melanoma Samples from Variable Anatomic Sites. Clinical Cancer Research 2015, 21: 3052-3060. PMID: 25788491, PMCID: PMC4490112, DOI: 10.1158/1078-0432.ccr-14-3073.Peer-Reviewed Original ResearchConceptsPD-L1 expressionT-cell contentPD-1/PD-L1 inhibitorsHigher T-cell contentT-cell infiltratesPD-L1 inhibitorsAnatomic sitesBrain metastasesMetastatic melanomaTissue microarrayHigh PD-L1 expressionLess PD-L1 expressionLow PD-L1 expressionTumor PD-L1 expressionHigher TIL contentImproved overall survivalT cell infiltrationLess T cellsMetastatic melanoma samplesExtracerebral metastasesCerebral metastasesOverall survivalDermal metastasesImproved survivalPD-L1
2008
Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer
Nadler Y, Camp RL, Giltnane JM, Moeder C, Rimm DL, Kluger HM, Kluger Y. Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer. Breast Cancer Research 2008, 10: r35. PMID: 18430249, PMCID: PMC2397537, DOI: 10.1186/bcr1998.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsBiomarkers, TumorBreast NeoplasmsDNA-Binding ProteinsDrug Resistance, NeoplasmFemaleFluorescent Antibody TechniqueFollow-Up StudiesGene Expression Regulation, NeoplasticHumansImmunohistochemistryKaplan-Meier EstimateLymphatic MetastasisMiddle AgedPredictive Value of TestsPrognosisProportional Hazards ModelsProtein Array AnalysisProto-Oncogene Proteins c-bcl-2Receptors, EstrogenReceptors, ProgesteroneTranscription FactorsTreatment OutcomeConceptsNode-positive subsetHER2/neuProgesterone receptorBreast cancerEstrogen receptorBcl-2 expressionBAG-1 expressionImproved survivalBcl-2Anti-apoptotic mediator Bcl-2Breast tumorsSteroid receptor positivitySubset of patientsBAG-1Antihormonal therapyFavorable prognosisReceptor positivityMultivariable analysisPathological variablesEntire cohortPrognostic valuePrognostic markerImproved outcomesLarge cohortClinical development
2005
Automated Quantitative Analysis of E-Cadherin Expression in Lymph Node Metastases Is Predictive of Survival in Invasive Ductal Breast Cancer
Harigopal M, Berger AJ, Camp RL, Rimm DL, Kluger HM. Automated Quantitative Analysis of E-Cadherin Expression in Lymph Node Metastases Is Predictive of Survival in Invasive Ductal Breast Cancer. Clinical Cancer Research 2005, 11: 4083-4089. PMID: 15930343, DOI: 10.1158/1078-0432.ccr-04-2191.Peer-Reviewed Original ResearchConceptsE-cadherin expressionLymph node metastasisNodal metastasisBreast cancerImproved survivalNode metastasisTissue microarrayNode-positive breast cancerInvasive ductal breast cancerHER2/neu statusAnti-invasive roleInvasive ductal tumorsNode-positive patientsDuctal breast cancerSubset of patientsGood prognostic markerAggressive tumor behaviorStrong E-cadherin expressionHigh E-cadherin expressionCy5-conjugated antibodiesDuctal tumorsMetastatic sitesPrognostic valueTumor sizePrimary tumor