2021
Spatially resolved analysis of the T cell immune contexture in lung cancer-associated brain metastases
Lu BY, Gupta R, Aguirre-Ducler A, Gianino N, Wyatt H, Ribeiro M, Chiang VL, Contessa JN, Adeniran AJ, Jilaveanu LB, Kluger HM, Schalper KA, Goldberg SB. Spatially resolved analysis of the T cell immune contexture in lung cancer-associated brain metastases. Journal For ImmunoTherapy Of Cancer 2021, 9: e002684. PMID: 34670827, PMCID: PMC8529973, DOI: 10.1136/jitc-2021-002684.Peer-Reviewed Original ResearchConceptsPrimary lung tumorsT cell subsetsMajor T cell subsetsMultiplexed quantitative immunofluorescenceLung tumorsT cellsCoinhibitory receptorsTim-3Cell subsetsBrain metastasesQuantitative immunofluorescenceHigh LAG-3 expressionTumor PD-L1 expressionPD-L1 protein expressionLymphocyte activation gene-3Low T cell infiltrationHigh TIM-3Major clinicopathological variablesPD-L1 expressionLAG-3 expressionT cell infiltrationTumor-infiltrating lymphocytesLonger overall survivalCell death 1Tumor immune microenvironmentA Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1
Weiss SA, Djureinovic D, Jessel S, Krykbaeva I, Zhang L, Jilaveanu L, Ralabate A, Johnson B, Levit NS, Anderson G, Zelterman D, Wei W, Mahajan A, Trifan O, Bosenberg M, Kaech SM, Perry CJ, Damsky W, Gettinger S, Sznol M, Hurwitz M, Kluger HM. A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1. Clinical Cancer Research 2021, 27: 4757-4767. PMID: 34140403, PMCID: PMC9236708, DOI: 10.1158/1078-0432.ccr-21-0903.Peer-Reviewed Original ResearchConceptsAnti-PD-1/PD-L1Non-small cell lung cancerCell lung cancerRenal cell carcinomaPD-L1Lung cancerDisease progressionCommon treatment-related adverse eventsPD-1/PD-L1 inhibitorsTreatment-related adverse eventsPhase 2 doseSubstantial clinical challengeUnconfirmed partial responseDose-limiting toxicityPD-L1 inhibitorsPhase I trialDose-escalation designPro-inflammatory cytokinesMultiple tumor typesAsymptomatic elevationStable diseaseIntolerable toxicityAdverse eventsMedian durationPartial response
2019
Perilesional 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 tumors
2016
Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial
Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, Tsiouris AJ, Cohen J, Vortmeyer A, Jilaveanu L, Yu J, Hegde U, Speaker S, Madura M, Ralabate A, Rivera A, Rowen E, Gerrish H, Yao X, Chiang V, Kluger HM. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2016, 17: 976-983. PMID: 27267608, PMCID: PMC5526047, DOI: 10.1016/s1470-2045(16)30053-5.Peer-Reviewed Original ResearchConceptsProgressive brain metastasesUntreated brain metastasesBrain metastasis responseYale Cancer CenterBrain metastasesPhase 2 trialCell lung cancerAdverse eventsMetastasis responseCancer CenterLung cancerMelanoma cohortGrade 3 colitisGrade 3 fatigueGrade 3 pneumonitisPD-1 axisAcute kidney injuryNeurological adverse eventsPD-1 inhibitorsAcceptable safety profilePD-L1 expressionSystemic immunotherapyKidney injuryPrimary endpointNSCLC cohort
2012
Multi-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells
Zito CR, Jilaveanu LB, Anagnostou V, Rimm D, Bepler G, Maira SM, Hackl W, Camp R, Kluger HM, Chao HH. Multi-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells. PLOS ONE 2012, 7: e31331. PMID: 22355357, PMCID: PMC3280285, DOI: 10.1371/journal.pone.0031331.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic AgentsBlotting, WesternCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellCell Line, TumorCell ProliferationClass Ia Phosphatidylinositol 3-KinaseDrug SynergismFemaleFluorescent Antibody TechniqueHumansImmunoenzyme TechniquesLung NeoplasmsMaleMiddle AgedPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktSignal TransductionTissue Array AnalysisTOR Serine-Threonine KinasesConceptsNon-small cell lung cancerNSCLC cell linesDual PI3K/mTOR inhibitorPI3K/AKT/mTOR pathwayPI3K/mTOR inhibitorAKT/mTOR pathwayPI3K inhibitorsNVP-BEZ235MTOR inhibitorsNVP-BKM120MTOR expressionAdvanced stageCell linesMTOR pathwayPI3K subunitsNon-small cell lung cancer cellsK inhibitorsCell lung cancer cellsCell lung cancerSquamous cell carcinomaP85 expressionSynergistic growth inhibitionRegulation of pAktExpression of p85Lung cancer cells