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
Melanoma brain metastases have lower T-cell content and microvessel density compared to matched extracranial metastases
Weiss SA, Zito C, Tran T, Heishima K, Neumeister V, McGuire J, Adeniran A, Kluger H, Jilaveanu LB. Melanoma brain metastases have lower T-cell content and microvessel density compared to matched extracranial metastases. Journal Of Neuro-Oncology 2020, 152: 15-25. PMID: 32974852, PMCID: PMC7910371, DOI: 10.1007/s11060-020-03619-0.Peer-Reviewed Original ResearchConceptsT-cell contentMelanoma brain metastasesPD-L1 expressionLower microvessel densityMicrovessel densityBrain metastasesExtracranial metastasesMacrophage contentB cellsProspective therapeutic clinical trialsTumor-infiltrating T cellsImmune-modulating drugsImmune cell subsetsTherapeutic clinical trialsExtracerebral metastasesHigh CD68Low CD3Low CD8Systemic therapyIntracerebral metastasesMetastatic sitesCell subsetsMetastatic melanomaImmune cellsClinical trials
2019
Brain Metastasis From Renal-Cell Carcinoma: An Institutional Study
Suarez-Sarmiento A, Nguyen KA, Syed JS, Nolte A, Ghabili K, Cheng M, Liu S, Chiang V, Kluger H, Hurwitz M, Shuch B. Brain Metastasis From Renal-Cell Carcinoma: An Institutional Study. Clinical Genitourinary Cancer 2019, 17: e1163-e1170. PMID: 31519468, DOI: 10.1016/j.clgc.2019.08.006.Peer-Reviewed Original ResearchConceptsRCC brain metastasesRecurrence-free survivalRenal cell carcinomaBrain metastasesOverall survivalClinical trialsAdvanced renal cell carcinomaCentral nervous system treatmentClear cell renal cell carcinomaMedian overall survivalSingle institution experienceGood local controlKaplan-Meier methodAggressive therapyCNS recurrenceTreatment eraCumulative incidenceExtracranial metastasesMetastatic diseaseSystemic therapyInitial presentationLocal therapyClinical symptomsRCC patientsCell carcinomaPerilesional edema in brain metastases: potential causes and implications for treatment with immune therapy
Tran TT, Mahajan A, Chiang VL, Goldberg SB, Nguyen DX, Jilaveanu LB, Kluger HM. Perilesional edema in brain metastases: potential causes and implications for treatment with immune therapy. Journal For ImmunoTherapy Of Cancer 2019, 7: 200. PMID: 31362777, PMCID: PMC6668163, DOI: 10.1186/s40425-019-0684-z.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntravenousAntibodies, Monoclonal, HumanizedAntigens, CD34Antineoplastic Agents, ImmunologicalBlood-Brain BarrierBrain EdemaBrain NeoplasmsCarcinoma, Non-Small-Cell LungClinical Trials, Phase II as TopicDrug Administration ScheduleHumansLung NeoplasmsMelanomaRetrospective StudiesTight JunctionsTreatment OutcomeTumor Cells, CulturedConceptsMelanoma brain metastasesBrain metastasesPerilesional edemaVessel densityEdema volumeSensitive tumorsBlood-brain barrier model systemNon-small cell lungTight junction resistancePhase II clinical trialSignificant perilesional edemaUntreated brain metastasesBlood-brain barrierPre-clinical modelsDegree of edemaTumor mass effectPotential causesMelanoma brainShort-term cultureExtracranial metastasesImmune therapyMelanoma patientsSignificant morbidityCell lungLarge tumorsFunctional profile and clinical significance of major tumor infiltrating lymphocyte subsets in lung cancer-associated brain metastases.
Lu B, Gupta R, Stewart T, Kluger H, Jilaveanu L, Schalper K, Goldberg S. Functional profile and clinical significance of major tumor infiltrating lymphocyte subsets in lung cancer-associated brain metastases. Journal Of Clinical Oncology 2019, 37: 2066-2066. DOI: 10.1200/jco.2019.37.15_suppl.2066.Peer-Reviewed Original ResearchPrimary lung tumorsMajor T cell subsetsMultiplexed quantitative immunofluorescenceT cell subsetsExtracranial metastasesT cellsLung tumorsBrain metastasesQuantitative immunofluorescenceAdaptive anti-tumor responsesLow T cell infiltrationMajor clinicopathologic variablesYale Cancer CenterAdaptive immune cellsRegulatory T cellsT cell infiltrationAnti-tumor responseLonger overall survivalOptimal treatment strategyLung cancer patientsKi-67 levelsLung cancer histologyLymphocyte subsetsOverall survivalPrimary malignancy