2021
Circulating 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
2019
Safety, Clinical Activity, and Biological Correlates of Response in Patients with Metastatic Melanoma: Results from a Phase I Trial of Atezolizumab
Hamid O, Molinero L, Bolen CR, Sosman JA, Muñoz-Couselo E, Kluger HM, McDermott DF, Powderly J, Sarkar I, Ballinger M, Fassò M, O'Hear C, Chen DS, Hegde PS, Hodi FS. Safety, Clinical Activity, and Biological Correlates of Response in Patients with Metastatic Melanoma: Results from a Phase I Trial of Atezolizumab. Clinical Cancer Research 2019, 25: 6061-6072. PMID: 31358540, DOI: 10.1158/1078-0432.ccr-18-3488.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorFatigueFemaleFeverFollow-Up StudiesHumansMaleMelanomaMiddle AgedPrognosisProgression-Free SurvivalPruritusRetrospective StudiesSeverity of Illness IndexSkinSkin NeoplasmsT-Lymphocytes, CytotoxicTranscriptomeYoung AdultConceptsTreatment-related adverse eventsAdverse eventsOverall survivalMetastatic melanomaCommon treatment-related adverse eventsMost treatment-related adverse eventsAntitumor T-cell activityMeaningful long-term survivalActivity of atezolizumabEfficacy-evaluable patientsPhase Ia studyTreatment-related deathsMedian overall survivalPD-L1 expressionProgression-free survivalCohort of patientsPhase I trialT cell activityOverall response rateBiological correlatesLong-term safetyLong-term survivalPrimary study objectiveDurable responsesGrade 1/2Transcriptomic 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 cellsHallmarkTranscriptomeCells
2015
PLEKHA5 as a Biomarker and Potential Mediator of Melanoma Brain Metastasis
Jilaveanu LB, Parisi F, Barr ML, Zito CR, Cruz-Munoz W, Kerbel RS, Rimm DL, Bosenberg MW, Halaban R, Kluger Y, Kluger HM. PLEKHA5 as a Biomarker and Potential Mediator of Melanoma Brain Metastasis. Clinical Cancer Research 2015, 21: 2138-2147. PMID: 25316811, PMCID: PMC4397107, DOI: 10.1158/1078-0432.ccr-14-0861.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBrain NeoplasmsCell Line, TumorFemaleFluorescent Antibody TechniqueGene Expression ProfilingHumansImage Processing, Computer-AssistedIntracellular Signaling Peptides and ProteinsMaleMelanomaMiddle AgedNeoplasm InvasivenessTissue Array AnalysisTranscriptomeYoung AdultConceptsCell line modelsBlood-brain barrierBrain metastasesGene expression profilesGene expression profilingExpression profilingExpression profilesPLEKHA5Brain metastasis-free survivalA375P cellsQuantitative immunofluorescenceEarly brain metastasisMelanoma brain metastasesMetastasis-free survivalProfile of patientsPotential mediatorsProtein levelsMetastatic melanoma casesEarly developmentMelanoma cellsKnockdownDecrease proliferationBBB transmigrationExtracerebral sitesMetastatic sites