2024
TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3
Perales O, Jilaveanu L, Adeniran A, Su D, Hurwitz M, Braun D, Kluger H, Schoenfeld D. TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3. Cancer Immunology, Immunotherapy 2024, 73: 192. PMID: 39105820, PMCID: PMC11303630, DOI: 10.1007/s00262-024-03773-8.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaRenal cell carcinoma tumorsT cellsTIGIT expressionCheckpoint inhibitorsPD-1Likelihood of response to therapyTumor-infiltrating T cellsCD3+ T cellsRenal cell carcinoma metastasisTreatment of renal cell carcinomaImmune checkpoint inhibitorsInfiltrating T cellsPurposeImmune checkpoint inhibitorsResponse to therapyT cell immunoglobulinCD3+ levelsMetastatic RCC specimensAdjacent normal renal tissuesNormal renal tissuesQuantitative immunofluorescence analysisCell carcinomaResistant diseasePotential therapeutic targetTissue microarrayMelanocortin-1 Receptor Expression as a Marker of Progression in Melanoma
Su D, Djureinovic D, Schoenfeld D, Marquez-Nostra B, Olino K, Jilaveanu L, Kluger H. Melanocortin-1 Receptor Expression as a Marker of Progression in Melanoma. JCO Precision Oncology 2024, 8: e2300702. PMID: 38662983, PMCID: PMC11513442, DOI: 10.1200/po.23.00702.Peer-Reviewed Original ResearchConceptsMC1R expressionMelanoma progressionAssociated with shorter survivalStages of melanoma progressionCases of benign neviChronic sun exposureMarkers of progressionHuman melanoma tissuesBreslow thicknessMelanocortin-1Metastatic melanomaOverall survivalPrimary melanomaMetastatic tumorsMelanoma cohortReceptor expressionPredictive biomarkersAggressive melanomaPrimary lesionTissue microarrayShorter survivalMale sexQuantitative immunofluorescenceBenign neviClinical trials
2023
Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases
Schoenfeld D, Moutafi M, Martinez S, Djureinovic D, Merkin R, Adeniran A, Braun D, Signoretti S, Choueiri T, Parisi F, Hurwitz M, Rimm D, Wei W, Jilaveanu L, Kluger H. Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases. Journal For ImmunoTherapy Of Cancer 2023, 11: e007240. PMID: 37586773, PMCID: PMC10432651, DOI: 10.1136/jitc-2023-007240.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaBrain metastasesPrimary tumorTumor microenvironmentDigital spatial profilingCell carcinomaActivation protein expressionInflammatory macrophage markersRCC brain metastasesInnate immune activatorsNormal kidney samplesProgressive stagesExtracranial metastasesTim-3Immune checkpointsImmune dysfunctionImmune activationRCC metastasisLonger survivalImmune activatorsMacrophage markersTreatment responseSeparate cohortTissue microarrayMetastatic samples
2020
Quantitative analysis of CMTM6 expression in tumor microenvironment in metastatic melanoma and association with outcome on immunotherapy
Martinez-Morilla S, Zugazagoitia J, Wong PF, Kluger HM, Rimm DL. Quantitative analysis of CMTM6 expression in tumor microenvironment in metastatic melanoma and association with outcome on immunotherapy. OncoImmunology 2020, 10: 1864909. PMID: 33457084, PMCID: PMC7781756, DOI: 10.1080/2162402x.2020.1864909.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsPD-L1CMTM6 expressionControl patientsLonger survivalTissue microarrayQuantitative immunofluorescenceEffectiveness of immunotherapyMetastatic melanoma patientsDeath ligand 1Like MARVEL transmembrane domainCancer Genome Atlas (TCGA) databaseExpression of CMTM6MARVEL transmembrane domainExpression of mRNAChemokine-like factorICI treatmentCheckpoint inhibitorsPretreatment biopsiesCD68 markersImmune compartmentMultivariable analysisMelanoma patientsImmune-related proteinsPredictive factors
2019
High-Plex Predictive Marker Discovery for Melanoma Immunotherapy–Treated Patients Using Digital Spatial Profiling
Toki MI, Merritt CR, Wong PF, Smithy JW, Kluger HM, Syrigos KN, Ong GT, Warren SE, Beechem JM, Rimm DL. High-Plex Predictive Marker Discovery for Melanoma Immunotherapy–Treated Patients Using Digital Spatial Profiling. Clinical Cancer Research 2019, 25: 5503-5512. PMID: 31189645, PMCID: PMC6744974, DOI: 10.1158/1078-0432.ccr-19-0104.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBiomarkers, TumorFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryImmunotherapyLymphocytes, Tumor-InfiltratingMaleMelanomaMolecular Diagnostic TechniquesMolecular Targeted TherapyPrognosisProportional Hazards ModelsTissue Array AnalysisTreatment OutcomeConceptsNon-small cell lung cancerProlonged progression-free survivalDigital spatial profilingOverall survivalPD-L1Predictive markerPD-L1 expressionProgression-free survivalProtein expressionCell lung cancerNovel predictive markerCD68-positive cellsStromal CD3Melanoma immunotherapyImmune markersImmune therapyPrognostic valueLung cancerAntibody cocktailTissue microarrayQuantitative fluorescenceOutcome assessmentTumor cellsHigh concordanceMultiple biomarkers
2017
PD-L1 Studies Across Tumor Types, Its Differential Expression and Predictive Value in Patients Treated with Immune Checkpoint Inhibitors
Kluger HM, Zito CR, Turcu G, Baine M, Zhang H, Adeniran A, Sznol M, Rimm DL, Kluger Y, Chen L, Cohen JV, Jilaveanu LB. PD-L1 Studies Across Tumor Types, Its Differential Expression and Predictive Value in Patients Treated with Immune Checkpoint Inhibitors. Clinical Cancer Research 2017, 23: 4270-4279. PMID: 28223273, PMCID: PMC5540774, DOI: 10.1158/1078-0432.ccr-16-3146.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerPD-L1 expressionRenal cell carcinomaPD-1 inhibitorsCell carcinomaImmune-infiltrating cellsMelanoma patientsPD-L1Tumor cellsTumor typesTumor-associated inflammatory cellsCTLA-4 inhibitorsCell lung cancerRenal cell carcinoma cellsHigh response rateClin Cancer ResCell linesMelanoma tumor cellsPD-1Multivariable analysisNSCLC specimensInflammatory cellsLung cancerTissue microarrayResponse rate
2015
MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors
Shuch B, Falbo R, Parisi F, Adeniran A, Kluger Y, Kluger HM, Jilaveanu LB. MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors. BioMed Research International 2015, 2015: 192406. PMID: 26448928, PMCID: PMC4584049, DOI: 10.1155/2015/192406.Peer-Reviewed Original ResearchConceptsClear cell renal cell carcinomaCell renal cell carcinomaMetastatic sitesRenal cell carcinomaMET expressionCell carcinomaPredictive biomarkersPrimary tumorMetastatic clear cell renal cell carcinomaMetastatic kidney cancerAppropriate patient selectionDistant metastatic sitesPatient selectionMetastatic tissuesKidney cancerMET pathwayTissue microarrayBiomarker assessmentNumber of casesPrimary siteModerate concordancePathway inhibitorTumorsDistant tissuesNephrectomyCharacterization 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
2014
PAX-8 expression in renal tumours and distant sites: A useful marker of primary and metastatic renal cell carcinoma?
Barr ML, Jilaveanu LB, Camp RL, Adeniran AJ, Kluger HM, Shuch B. PAX-8 expression in renal tumours and distant sites: A useful marker of primary and metastatic renal cell carcinoma? Journal Of Clinical Pathology 2014, 68: 12. PMID: 25315900, PMCID: PMC4429054, DOI: 10.1136/jclinpath-2014-202259.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaPAX-8 expressionMetastatic renal cell carcinomaRenal tumorsMetastatic sitesCell carcinomaClear cell renal cell carcinomaPAX-8 stainingCell renal cell carcinomaPAX-8Distant sitesNormal renal tissueUseful diagnostic markerAdjacent normal kidneyHistological typePrimary tumorDistant tumorsLack of expressionRenal originImmunohistochemical stainsChromophobe tumorsClear cellsRenal tissueNormal kidneyTissue microarrayPD-L1 Expression in Clear Cell Renal Cell Carcinoma: An Analysis of Nephrectomy and Sites of Metastases
Jilaveanu LB, Shuch B, Zito CR, Parisi F, Barr M, Kluger Y, Chen L, Kluger HM. PD-L1 Expression in Clear Cell Renal Cell Carcinoma: An Analysis of Nephrectomy and Sites of Metastases. Journal Of Cancer 2014, 5: 166-172. PMID: 24563671, PMCID: PMC3931264, DOI: 10.7150/jca.8167.Peer-Reviewed Original ResearchPD-L1 expressionMetastatic sitesPD-L1Tissue microarrayMetastatic specimensTumor PD-L1 expressionClear cell renal cell carcinomaPD-1 inhibitorsAutomated Quantitative AnalysisMetastatic RCC patientsCell renal cell carcinomaSite of metastasisRenal cell carcinomaClear cell RCCRenal cell carcinoma cellsInter-tumor heterogeneityRCC patientsCell carcinomaNephrectomy specimensTumor expressionCore biopsyImmune escapeCell RCCBiopsy coresClinical development
2012
c-Met is a prognostic marker and potential therapeutic target in clear cell renal cell carcinoma
Gibney GT, Aziz SA, Camp RL, Conrad P, Schwartz BE, Chen CR, Kelly WK, Kluger HM. c-Met is a prognostic marker and potential therapeutic target in clear cell renal cell carcinoma. Annals Of Oncology 2012, 24: 343-349. PMID: 23022995, PMCID: PMC3551486, DOI: 10.1093/annonc/mds463.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsBiomarkers, TumorCarcinoma, Renal CellCell Line, TumorCell ProliferationFemaleHepatocyte Growth FactorHumansIndolesKidney NeoplasmsMaleMiddle AgedPiperazinesPrognosisProto-Oncogene Proteins c-metPyrrolidinonesQuinolinesSulfonamidesTissue Array AnalysisConceptsRenal cell carcinomaClear cell renal cell carcinomaC-Met expressionCell renal cell carcinomaHigh c-Met expressionAdjacent normal renal tissuesNormal renal tissueARQ 197Cell carcinomaRenal tissueRCC tumorsTissue microarrayWorse disease-specific survivalC-MetClear cell RCC cell linesC-Met protein expressionCell linesPoor pathologic featuresCell subset analysisDisease-specific survivalPapillary renal cell carcinomaRange of malignanciesC-Met pathwayC-Met inhibitionPotential therapeutic targetCD70 expression patterns in renal cell carcinoma
Jilaveanu LB, Sznol J, Aziz SA, Duchen D, Kluger HM, Camp RL. CD70 expression patterns in renal cell carcinoma. Human Pathology 2012, 43: 1394-1399. PMID: 22401771, PMCID: PMC3374042, DOI: 10.1016/j.humpath.2011.10.014.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaCell carcinomaCD70 expressionPapillary tumorsHigh CD70 expressionExpression of CD70Clear cell tumorsNovel therapeutic agentsRenal cell carcinoma specimensPathologic variablesHistologic subtypePrognostic valueCell subsetsCell tumorsUnivariate analysisClinical trialsImmune escapeSitu protein expressionT lymphocytesClear cellsTissue microarrayCarcinoma specimensCD70Immunohistochemistry-based methodMultivariate analysis
2011
Characterization and targeting of phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in renal cell cancer
Elfiky AA, Aziz SA, Conrad PJ, Siddiqui S, Hackl W, Maira M, Robert CL, Kluger HM. Characterization and targeting of phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in renal cell cancer. Journal Of Translational Medicine 2011, 9: 133. PMID: 21834980, PMCID: PMC3173341, DOI: 10.1186/1479-5876-9-133.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisAutomationBiomarkers, TumorCarcinoma, Renal CellCell Line, TumorChromonesDrug SynergismHumansImidazolesInhibitory Concentration 50Kidney NeoplasmsMolecular Targeted TherapyMorpholinesMultivariate AnalysisPhosphatidylinositol 3-KinasePhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsQuinolinesSirolimusTOR Serine-Threonine KinasesConceptsRenal cell carcinomaRCC cell linesNVP-BEZ235PI3KMTOR expressionMetastatic renal cell carcinomaPI3K subunitsHigh mTOR expressionAutomated Quantitative AnalysisRCC cell growthRenal cell cancerExpression of p85PI3K inhibitor LY294002Cell linesWarrants further investigationK inhibitor LY294002PI3K inhibitorsMulti-variable analysisCell cancerCell carcinomaClinical trialsSitu protein expressionNephrectomy casesTissue microarrayMTOR inhibitors
2010
A Role for ATF2 in Regulating MITF and Melanoma Development
Shah M, Bhoumik A, Goel V, Dewing A, Breitwieser W, Kluger H, Krajewski S, Krajewska M, DeHart J, Lau E, Kallenberg DM, Jeong H, Eroshkin A, Bennett DC, Chin L, Bosenberg M, Jones N, Ronai ZA. A Role for ATF2 in Regulating MITF and Melanoma Development. PLOS Genetics 2010, 6: e1001258. PMID: 21203491, PMCID: PMC3009656, DOI: 10.1371/journal.pgen.1001258.Peer-Reviewed Original ResearchConceptsMelanoma developmentMouse melanoma modelHuman melanoma cell linesMITF expressionMelanoma tissue microarrayMelanoma cell linesMetastatic diseasePoor prognosisTissue microarrayXenograft modelMelanoma modelPrimary specimensPrimary human melanocytesOncogenic BRAFMiceGene expression profilingHigh MITF expressionDependent suppressionATF2 knockdownCell linesSoft agarHuman melanocytesMelanocytesMelanoma susceptibilityPrimary melanocytes
2009
Growth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer
Nadler Y, González AM, Camp RL, Rimm DL, Kluger HM, Kluger Y. Growth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer. Annals Of Oncology 2009, 21: 466-473. PMID: 19717535, PMCID: PMC2826097, DOI: 10.1093/annonc/mdp346.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBlotting, WesternBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, LobularFemaleFluorescent Antibody TechniqueFollow-Up StudiesGRB7 Adaptor ProteinHumansImage Processing, Computer-AssistedMiddle AgedPrognosisReceptor, ErbB-2Survival RateTissue Array AnalysisTumor Cells, CulturedYoung AdultConceptsHER2/neuBreast cancerPrognostic markerHER2/neu-positive breast cancerGRB7 expressionHigh HER2/neuNeu-positive breast cancerHER2/neu overexpressionPrimary breast cancerBreast cancer patientsIndependent prognostic markerNode-positive subsetValuable prognostic markerProtein 7Cy5-conjugated antibodiesMultivariable analysisWorse prognosisEntire cohortCancer patientsNeu overexpressionTissue microarrayTherapeutic targetCancerNeuPatients
2008
Assessing Expression of Apoptotic Markers Using Large Cohort Tissue Microarrays
Pick E, McCarthy MM, Kluger HM. Assessing Expression of Apoptotic Markers Using Large Cohort Tissue Microarrays. Methods In Molecular Biology 2008, 414: 83-93. PMID: 18175814, DOI: 10.1007/978-1-59745-339-4_8.Peer-Reviewed Original ResearchConceptsLarge cohortApoptotic markersParaffin-embedded specimensHundreds of patientsAnti-apoptotic elementsTissue microarray technologySitu protein expressionApoptotic marker expressionTissue microarrayMarker expressionBenign cellsImmunohistochemistryProtein expressionExtrinsic pathwayExpression levelsCohortMarkersExpressionCellsPatients
2007
The X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with Carboplatin sensitization
Kluger HM, McCarthy MM, Alvero AB, Sznol M, Ariyan S, Camp RL, Rimm DL, Mor G. The X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with Carboplatin sensitization. Journal Of Translational Medicine 2007, 5: 6. PMID: 17257402, PMCID: PMC1796544, DOI: 10.1186/1479-5876-5-6.Peer-Reviewed Original ResearchConceptsMetastatic melanomaXIAP expressionCell linesCy5-conjugated antibodiesMechanism of actionMelanoma cell linesPrimary lesionOvarian cancerTherapeutic approachesTissue microarrayDisease aggressionCarboplatin sensitivityChemotherapy resistanceMalignant progressionClinical specimensBenign counterpartsCarboplatinMelanomaChemotherapy sensitizationPrimary specimensPhenoxodiolResistant cellsMelanoma cellsHigh expressionMelanoma resistance
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
2004
Automated Quantitative Analysis of Tissue Microarrays Reveals an Association between High Bcl-2 Expression and Improved Outcome in Melanoma
DiVito KA, Berger AJ, Camp RL, Dolled-Filhart M, Rimm DL, Kluger HM. Automated Quantitative Analysis of Tissue Microarrays Reveals an Association between High Bcl-2 Expression and Improved Outcome in Melanoma. Cancer Research 2004, 64: 8773-8777. PMID: 15574790, DOI: 10.1158/0008-5472.can-04-1387.Peer-Reviewed Original ResearchConceptsBcl-2 expressionHigh Bcl-2 expressionTissue microarrayMetastatic specimensResponse rateSmall cohortProgression-free survivalImproved response ratesLarge patient cohortMelanoma patientsClark levelEntire cohortBreslow depthClinical variablesPatient cohortMetastatic melanomaContinuous index scoreBetter outcomesIndex scoreMelanoma specimensCohortMelanomaBcl-2PatientsOutcomes