2022
Inhibition of renalase drives tumour rejection by promoting T cell activation
Guo X, Jessel S, Qu R, Kluger Y, Chen TM, Hollander L, Safirstein R, Nelson B, Cha C, Bosenberg M, Jilaveanu LB, Rimm D, Rothlin CV, Kluger HM, Desir GV. Inhibition of renalase drives tumour rejection by promoting T cell activation. European Journal Of Cancer 2022, 165: 81-96. PMID: 35219026, PMCID: PMC8940682, DOI: 10.1016/j.ejca.2022.01.002.Peer-Reviewed Original ResearchConceptsPD-1 inhibitorsMurine melanoma modelMelanoma-bearing miceMelanoma modelTumor microenvironmentTumor rejectionCell death protein 1 (PD-1) inhibitorsAnti-PD-1 activityEnhanced T cell infiltrationT cell-dependent fashionMelanoma cellsMelanoma tumor regressionPreclinical melanoma modelsT cell infiltrationNatural killer cellsForkhead box P3Expression of IFNγWild-type miceProtein 1 inhibitorT cell activationTumor cell contentWild-type melanoma cellsCD4 cellsAdvanced melanomaAntibody treatment
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 microenvironmentIntratumour microbiome associated with the infiltration of cytotoxic CD8+ T cells and patient survival in cutaneous melanoma
Zhu G, Su H, Johnson CH, Khan SA, Kluger H, Lu L. Intratumour microbiome associated with the infiltration of cytotoxic CD8+ T cells and patient survival in cutaneous melanoma. European Journal Of Cancer 2021, 151: 25-34. PMID: 33962358, PMCID: PMC8184628, DOI: 10.1016/j.ejca.2021.03.053.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overBacteriaBacterial LoadBacterial TranslocationChemokinesClostridialesCytotoxicity, ImmunologicFemaleGastrointestinal MicrobiomeHumansLymphocyte CountLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedPrognosisSkin NeoplasmsT-Lymphocytes, CytotoxicTumor MicroenvironmentYoung AdultConceptsT cellsCutaneous melanomaPatient survivalGut microbiomeAdjusted hazard ratioT cell infiltrationChemokine gene expressionChemokine levelsCytotoxic CD8Hazard ratioSystemic inflammationShorter survivalCCL5 expressionPatient outcomesCD8Immune responseMortality riskGut microbiotaSurvival analysisMelanomaTumor nicheHuman cancersSurvivalSignificant correlationPositive association
2019
Functional 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
2017
Clinical results with combination of anti-CD27 agonist antibody, varlilumab, with anti-PD1 antibody nivolumab in advanced cancer patients.
Sanborn R, Pishvaian M, Kluger H, Callahan M, Weise A, Lutzky J, Yellin M, Rawls T, Vitale L, Halim A, Keler T, Davis T, Rizvi N. Clinical results with combination of anti-CD27 agonist antibody, varlilumab, with anti-PD1 antibody nivolumab in advanced cancer patients. Journal Of Clinical Oncology 2017, 35: 3007-3007. DOI: 10.1200/jco.2017.35.15_suppl.3007.Peer-Reviewed Original ResearchCRC patientsCancer patientsAnti-PD1 antibody nivolumabPD-1 inhibitor monotherapyCD8 T cell infiltrationDrug-related SAEsSerum chemokine levelsTarget lesion diametersAcute kidney injuryPD-L1 expressionPhase 2 studyAdvanced cancer patientsAnti-tumor immunityPost-treatment biopsiesSubset of patientsT cell infiltrationMotor-sensory neuropathyPhase 1 trialOptimal dosing strategiesPhase 2 cohortMajority of tumorsPhase 2 portionObjective PRsTreatment biopsiesChemokine levelsDistinct 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
2015
Characterization 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