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 biomarkersTranscriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis
Wingrove E, Liu ZZ, Patel KD, Arnal-Estapé A, Cai WL, Melnick MA, Politi K, Monteiro C, Zhu L, Valiente M, Kluger HM, Chiang VL, Nguyen DX. Transcriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis. Cell Reports 2019, 27: 1277-1292.e7. PMID: 31018140, PMCID: PMC6592283, DOI: 10.1016/j.celrep.2019.03.085.Peer-Reviewed Original ResearchConceptsBrain metastasesBrain tumor microenvironmentLineage programTumor microenvironmentTumor plasticityStromal gene expressionTranscriptomic hallmarksGene expressionTranscriptional hallmarksMultiple tumor typesMolecular landscapeStromal interactionsMajor siteIntact tissueNeuroinflammatory responseSyngeneic modelPatient biopsiesTumor typesMetastasisMalignant cellsDifferent subtypesTumor cellsHallmarkTranscriptomeCellsTranscriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis
Wingrove E, Liu Z, Patel K, Arnal‐Estape A, Melnick M, Politi K, Monteiro C, Zhu L, Valiente M, Kluger H, Chiang V, Nguyen D. Transcriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis. The FASEB Journal 2019, 33: 368.8-368.8. DOI: 10.1096/fasebj.2019.33.1_supplement.368.8.Peer-Reviewed Original ResearchBrain tumor microenvironmentBrain metastasesTumor microenvironmentTumor cellsLung adenocarcinomaTumor lesionsBrain metastatic tumor cellsBreast cancer brain metastasesHuman tumorsExpression of TIM3Cancer brain metastasesMetastatic brain tumorsExpression of astrocytesIntra-arterial injectionTumor-associated macrophagesSyngeneic model systemModels of melanomaFull-text articlesMetastatic tumor cellsCNS metastasesNeuroinflammatory responseBrain lesionsLung tumorsT cellsAthymic mice
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 rateDistinct dominant T-cell receptors with a tissue resident memory phenotype in individual melanoma metastases.
Dhodapkar K, Boddupalli C, Bar N, Kadaveru K, Krauthammer M, Pornputtapong N, Mai Z, Ariyan S, Narayan D, Kluger H, Deng Y, Verma R, Das R, Bacchiocchi A, Halaban R, Sznol M, Dhodapkar M. Distinct dominant T-cell receptors with a tissue resident memory phenotype in individual melanoma metastases. Journal Of Clinical Oncology 2017, 35: 3-3. DOI: 10.1200/jco.2017.35.7_suppl.3.Peer-Reviewed Original ResearchInhibitory immune checkpointsTissue-resident memory TT cellsIndividual metastasesMelanoma metastasesDominant T-cell receptorReduced T cell infiltrationTissue-resident memory phenotypeEffective anti-tumor immunityT-cell receptor sequencingTumor cellsExome sequencingResident memory phenotypeResident memory TT RM cellsAnti-tumor immunityT cell infiltrationCell receptor sequencingT cell subsetsAntibody-mediated blockadeT-cell contentVascular endothelial growth factorSingle-cell mass cytometryCell mass cytometryEndothelial growth factor
2016
Interlesional diversity of T cell receptors in melanoma with immune checkpoints enriched in tissue-resident memory T cells
Boddupalli CS, Bar N, Kadaveru K, Krauthammer M, Pornputtapong N, Mai Z, Ariyan S, Narayan D, Kluger H, Deng Y, Verma R, Das R, Bacchiocchi A, Halaban R, Sznol M, Dhodapkar MV, Dhodapkar KM. Interlesional diversity of T cell receptors in melanoma with immune checkpoints enriched in tissue-resident memory T cells. JCI Insight 2016, 1: e88955. PMID: 28018970, PMCID: PMC5161225, DOI: 10.1172/jci.insight.88955.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesMemory T cellsTissue-resident memory T cellsT cell receptorImmune checkpointsT cellsIndividual metastasesSubset of TILsExpression of ICsCell receptorTumor cellsLess IL-2Blood T cellsExpression of VEGFTIL infiltrationDurable responsesAdvanced melanomaImmune therapyNeoantigen loadIL-2Immune cellsNonlymphoid tissuesSame patientMyeloid cellsMetastasisRenalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism
Hollander L, Guo X, Velazquez H, Chang J, Safirstein R, Kluger H, Cha C, Desir G. Renalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism. Cancer Research 2016, 76: 3884-3894. PMID: 27197188, PMCID: PMC5031238, DOI: 10.1158/0008-5472.can-15-1524.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBiomarkers, TumorBlotting, WesternCase-Control StudiesCell CycleCell ProliferationFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticHumansImmunoenzyme TechniquesMacrophagesMaleMelanomaMiceMice, Inbred C57BLMice, NudeMonoamine OxidaseNeoplasm StagingP38 Mitogen-Activated Protein KinasesPrognosisProto-Oncogene Proteins c-aktSignal TransductionSTAT3 Transcription FactorSurvival RateTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsTumor-associated macrophagesDisease-specific survivalManagement of melanomaPotential therapeutic implicationsCell cycle inhibitor p21Melanoma cell growthPI3K/AktMelanoma cell survivalCell growth arrestPathogenic rolePrimary melanomaToxic injuryMurine xenograftsTherapeutic implicationsTumor growthClinical specimensRenalaseBax activationTumor microenvironmentTumor cellsInhibitor p21Growth arrestSurvival factorElevated expressionMAPK pathwayMelanoma Brain Metastasis Pseudoprogression after Pembrolizumab Treatment
Cohen JV, Alomari AK, Vortmeyer AO, Jilaveanu LB, Goldberg SB, Mahajan A, Chiang VL, Kluger HM. Melanoma Brain Metastasis Pseudoprogression after Pembrolizumab Treatment. Cancer Immunology Research 2016, 4: 179-182. PMID: 26701266, PMCID: PMC4881844, DOI: 10.1158/2326-6066.cir-15-0160.Peer-Reviewed Original ResearchConceptsCentral nervous systemBrain metastasesActive brain lesionsNew immunomodulating agentsImmune checkpoint inhibitorsRole of immunotherapyPembrolizumab treatmentCheckpoint inhibitorsCNS lesionsReactive astrocytosisImmune suppressionPerilesional edemaInflammatory cellsMicroglial cellsImmunomodulating agentMental statusBrain lesionsHistologic evaluationMost trialsNervous systemCentral enhancementTumor cellsPatientsMetastasisLesions
2015
Identification of Novel Radiosensitizers in a High-Throughput, Cell-Based Screen for DSB Repair Inhibitors
Goglia AG, Delsite R, Luz AN, Shahbazian D, Salem AF, Sundaram RK, Chiaravalli J, Hendrikx PJ, Wilshire JA, Jasin M, Kluger HM, Glickman JF, Powell SN, Bindra RS. Identification of Novel Radiosensitizers in a High-Throughput, Cell-Based Screen for DSB Repair Inhibitors. Molecular Cancer Therapeutics 2015, 14: 326-342. PMID: 25512618, PMCID: PMC4326563, DOI: 10.1158/1535-7163.mct-14-0765.Peer-Reviewed Original ResearchConceptsDSB repair inhibitorsDouble-strand breaksDSB repairHomologous recombinationRepair inhibitorsCell-based small molecule screenSuccessful DSB repairDNA-damaging agentsPlate-based formatCell-based screenSmall-molecule screenGenomic integrityTumor cell survivalMammalian cellsHR repairDNA repairMolecule screenReporter systemSecondary assaysCell survivalDNA damageCancer cell linesTumor cellsNovel hitsMost cancer therapies
2008
Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells
Kluger HM, Siddiqui SF, Angeletti C, Sznol M, Kelly WK, Molinaro AM, Camp RL. Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells. Laboratory Investigation 2008, 88: 962-972. PMID: 18626467, DOI: 10.1038/labinvest.2008.65.Peer-Reviewed Original Research