2024
TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial
Everson R, Hugo W, Sun L, Antonios J, Lee A, Ding L, Bu M, Khattab S, Chavez C, Billingslea-Yoon E, Salazar A, Ellingson B, Cloughesy T, Liau L, Prins R. TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial. Nature Communications 2024, 15: 3882. PMID: 38719809, PMCID: PMC11078958, DOI: 10.1038/s41467-024-48073-y.Peer-Reviewed Original ResearchConceptsAutologous tumor lysate-pulsed dendritic cellCD8+ T cellsT cellsPoly-ICLCTLR agonistsMalignant gliomasTumor lysate-pulsed dendritic cellsRandomized phase II trialCD4+ T cellsRandomized phase II clinical trialInterferon responsePhase II clinical trialPoly-ICLC treatmentDendritic cell vaccinesPD-1 expressionPhase II trialInterferon responsive gene expressionSystemic immune responsesImmune cell activationII clinical trialsInduction of interferon-inducible genesDelay disease progressionInterferon gene expressionInterferon-inducible genesPD-1
2022
Navigating an Internal Carotid Artery Anatomic Variant During Endovascular Therapy for Acute Ischemic Stroke
Peng T, Sharma R, Antonios J, Hebert R, Jasne A. Navigating an Internal Carotid Artery Anatomic Variant During Endovascular Therapy for Acute Ischemic Stroke. Stroke 2022, 53: e517-e518. PMID: 36106549, DOI: 10.1161/strokeaha.122.040501.Peer-Reviewed Case Reports and Technical Notes
2019
Expression of PD-1 by T Cells in Malignant Glioma Patients Reflects Exhaustion and Activation
Davidson T, Lee A, Hsu M, Sedighim S, Orpilla J, Treger J, Mastall M, Roesch S, Rapp C, Galvez M, Mochizuki A, Antonios J, Garcia A, Kotecha N, Bayless N, Nathanson D, Wang A, Everson R, Yong W, Cloughesy T, Liau L, Herold-Mende C, Prins R. Expression of PD-1 by T Cells in Malignant Glioma Patients Reflects Exhaustion and Activation. Clinical Cancer Research 2019, 25: 1913-1922. PMID: 30498094, PMCID: PMC6420851, DOI: 10.1158/1078-0432.ccr-18-1176.Peer-Reviewed Original ResearchConceptsPD-1<sup>+</sup> T cellsTumor-infiltrating lymphocytesPD-1<sup>+</sup> tumor-infiltrating lymphocytesPD-1 expressionPD-1T cellsPD-1<sup>+</supMalignant gliomasT lymphocytesEffective antitumor T-cell responsesExpression of markers of activationAntitumor T-cell responsesPD-1 blocking therapyExpression of PD-1Peripheral blood T lymphocytesExpressed PD-1PD-1/PD-L1T cell responsesBlood T lymphocytesIncreased proliferative capacityMarkers of activationPrimary malignant tumorHuman T lymphocytesHallmarks of memoryCentral nervous systemSPINT2 is hypermethylated in both IDH1 mutated and wild-type glioblastomas, and exerts tumor suppression via reduction of c-Met activation
Liu F, Cox C, Chowdhury R, Dovek L, Nguyen H, Li T, Li S, Ozer B, Chou A, Nguyen N, Wei B, Antonios J, Soto H, Kornblum H, Liau L, Prins R, Nghiemphu P, Yong W, Cloughesy T, Lai A. SPINT2 is hypermethylated in both IDH1 mutated and wild-type glioblastomas, and exerts tumor suppression via reduction of c-Met activation. Journal Of Neuro-Oncology 2019, 142: 423-434. PMID: 30838489, PMCID: PMC6516751, DOI: 10.1007/s11060-019-03126-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell ProliferationCpG IslandsDNA MethylationGene Expression Regulation, NeoplasticGlioblastomaHumansIsocitrate DehydrogenaseMembrane GlycoproteinsMiceMice, Inbred NODMice, SCIDMutationPromoter Regions, GeneticProto-Oncogene Proteins c-metTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsCpG islandsC-Met activationMethylation profilesGroup of CpG islandsDifferentially methylated CpG islandsIntegrated analysis of methylationAberrant CpG island hypermethylationAnalysis of methylationTargeted bisulfite sequencingCpG island hypermethylationCancer related genesTumor suppressor geneCohort of GBM samplesBisulfite sequencingGene regulationIDH1mut gliomasGene expressionRelated genesMethylation statusGlioblastoma cell lines in vitroPromoter hypermethylationTumor suppressionSPINT2DNMT1 knockdownFunctional consequencesImmunosuppressive mechanisms for stem cell transplant survival in spinal cord injury.
Antonios J, Farah G, Cleary D, Martin J, Ciacci J, Pham M. Immunosuppressive mechanisms for stem cell transplant survival in spinal cord injury. Neurosurgical FOCUS 2019, 46: e9. PMID: 30835678, DOI: 10.3171/2018.12.focus18589.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicAllograftsAnimalsBasiliximabCells, CulturedClinical Trials as TopicCyclosporineFemaleGraft RejectionGraft SurvivalGraft vs Host DiseaseHuman Embryonic Stem CellsHumansImmunosuppressive AgentsInduced Pluripotent Stem CellsMaleMiceMycophenolic AcidOligodendrocyte Precursor CellsRatsSpinal Cord InjuriesTacrolimusTransplantation, AutologousConceptsStem cell graftsSpinal cord injuryCell graftsSite of spinal cord injuryAcute spinal cord injuryCord injuryAdjuvant immunosuppressionClinically significant improvementImmunosuppressive mechanismsAdjuvant treatmentImmunological mechanismsTransplant survivalFunctional recoveryStandard intervention
2018
Cell-Based Immunotherapy of Gliomas
Everson R, Antonios J, Liau L. Cell-Based Immunotherapy of Gliomas. Progress In Neurological Surgery 2018, 32: 90-100. PMID: 29990977, DOI: 10.1159/000469683.Peer-Reviewed Original ResearchConceptsCellular immunotherapyImmune cellsDendritic cell (DC)-based vaccinesTreatment of malignant gliomasCellular immunotherapy approachesAntitumor immune cellsAntitumor responseAdoptive transferImmunotherapy approachesActive immunotherapyLive immune cellsMalignant gliomasEffector capabilitiesPassive immunotherapyImmunotherapyImmune responseEx vivoImmune systemGlioma cellsCell typesPatientsGliomaCellsNeoplasms
2017
Detection of immune responses after immunotherapy in glioblastoma using PET and MRI
Antonios J, Soto H, Everson R, Moughon D, Wang A, Orpilla J, Radu C, Ellingson B, Lee J, Cloughesy T, Phelps M, Czernin J, Liau L, Prins R. Detection of immune responses after immunotherapy in glioblastoma using PET and MRI. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 10220-10225. PMID: 28874539, PMCID: PMC5617282, DOI: 10.1073/pnas.1706689114.Peer-Reviewed Original ResearchConceptsPD-1Dendritic cellsMAb blockadeTumor lysate-pulsed DC vaccineHost antitumor immune responseTreated with dendritic cellsImmune responseDetection of immune responsesClinical management of patientsPET probeAntitumor immune responseTumor-infiltrating lymphocytesSyngeneic immunocompetent miceContrast enhancementSecondary lymphoid organsContrast-enhanced MRIManagement of patientsProbe uptakeNoninvasive imaging techniquesImmune inflammatory responseDC vaccinesImmunocompetent miceIntracranial tumorsImaging techniquesMalignant gliomasEpithelial membrane protein-2 (EMP2) promotes angiogenesis in glioblastoma multiforme
Qin Y, Takahashi M, Sheets K, Soto H, Tsui J, Pelargos P, Antonios J, Kasahara N, Yang I, Prins R, Braun J, Gordon L, Wadehra M. Epithelial membrane protein-2 (EMP2) promotes angiogenesis in glioblastoma multiforme. Journal Of Neuro-Oncology 2017, 134: 29-40. PMID: 28597184, PMCID: PMC5695892, DOI: 10.1007/s11060-017-2507-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD34Cell Line, TumorCell MovementFemaleGene Expression Regulation, NeoplasticGlioblastomaGreen Fluorescent ProteinsHuman Umbilical Vein Endothelial CellsHumansImmunoglobulin GMembrane GlycoproteinsMiceMice, NudeMicroarray AnalysisNeovascularization, PathologicRNA, Small InterferingTransfectionVascular Endothelial Growth Factor AXenograft Model Antitumor AssaysConceptsExpression of epithelial membrane protein-2Anti-angiogenic therapyEpithelial membrane protein-2Glioblastoma multiformeSurvival benefitAnti-vascular endothelial growth factor AProgression-free survival benefitReduction of tumor loadDecreased tumor vasculatureRecurrent glioblastoma multiformeVEGF-A levelsEndothelial growth factor AAbnormal blood vesselsProtein 2Malignant brain tumorsAggressive malignant brain tumorGrowth factor AHuman glioblastoma multiformePotential therapeutic effectsTumor loadTumor expressionPro-angiogenic effectsTumor vasculatureClinical prognosisVEGF-AImmunosuppressive tumor-infiltrating myeloid cells mediate adaptive immune resistance via a PD-1/PD-L1 mechanism in glioblastoma
Antonios J, Soto H, Everson R, Moughon D, Orpilla J, Shin N, Sedighim S, Treger J, Odesa S, Tucker A, Yong W, Li G, Cloughesy T, Liau L, Prins R. Immunosuppressive tumor-infiltrating myeloid cells mediate adaptive immune resistance via a PD-1/PD-L1 mechanism in glioblastoma. Neuro-Oncology 2017, 19: 796-807. PMID: 28115578, PMCID: PMC5464463, DOI: 10.1093/neuonc/now287.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalB7-H1 AntigenCancer VaccinesFemaleGlioblastomaHumansLymphocytes, Tumor-InfiltratingMiceMice, Inbred C57BLMyeloid CellsProgrammed Cell Death 1 ReceptorReceptor, Macrophage Colony-Stimulating FactorTumor Cells, CulturedTumor MicroenvironmentXenograft Model Antitumor AssaysConceptsTumor-infiltrating myeloid cellsAdaptive immune resistancePD-1 mAbCSF-1RiPD-1Immune resistancePD-L1Dendritic cellsMyeloid cellsColony stimulating factor 1 receptor inhibitorAnti-PD-1 monoclonal antibodyResponse to dendritic cellsIn vivo preclinical modelsPD-1 blockadePD-L1 expressionTumor-infiltrating lymphocytesPD-1/PD-L1Measured overall survivalSignificant survival benefitDevelopment of immune resistanceCytolysis in vitroLong-term survivalDC vaccinesTIL infiltrationOverall survival
2016
TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination
Hsu M, Sedighim S, Wang T, Antonios J, Everson R, Tucker A, Du L, Emerson R, Yusko E, Sanders C, Robins H, Yong W, Davidson T, Li G, Liau L, Prins R. TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination. Cancer Immunology Research 2016, 4: 412-418. PMID: 26968205, PMCID: PMC4873445, DOI: 10.1158/2326-6066.cir-15-0240.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesT cell receptorT-cell receptor sequencingImmune responseOverall survivalPeripheral bloodIncreased time to progressionTumour-infiltrating lymphocytes contentAssessment of tumor-infiltrating lymphocytesPredictors of immune responseAntigen-specific immune responsesTime to progressionDendritic cell immunotherapyDC vaccinesCell immunotherapyImmunotherapeutic strategiesSurvival outcomesStatistically significant correlationT cellsClinical outcomesAdjunctive treatmentBrain tumorsImmunotherapyNext-generation sequencing approachTumor
2015
Efficacy of systemic adoptive transfer immunotherapy targeting NY-ESO-1 for glioblastoma
Everson R, Antonios J, Lisiero D, Soto H, Scharnweber R, Garrett M, Yong W, Li N, Li G, Kruse C, Liau L, Prins R. Efficacy of systemic adoptive transfer immunotherapy targeting NY-ESO-1 for glioblastoma. Neuro-Oncology 2015, 18: 368-378. PMID: 26330563, PMCID: PMC4767237, DOI: 10.1093/neuonc/nov153.Peer-Reviewed Original ResearchConceptsNY-ESO-1NY-ESO-1-specific T cellsCells treated with decitabineDiffusely infiltrating tumor cellsAdoptive T cell therapyIntracranial human glioma xenograftsT-cell therapyDemethylating agent decitabineTumor rejection antigensGlioma-bearing miceSignificant survival benefitSquamous cell carcinomaPhenotype of lymphocytesT cell traffickingInfiltrating tumor cellsIdeal treatment modalityReal-time cytotoxicity assayHuman glioma xenograftsHuman glioblastoma cell culturesLong-term survivalClinically feasible strategyLong-term survival of animalsIn vitro treatmentTreatment of glioblastomaGlioblastoma cell culturespH-weighted molecular imaging of gliomas using amine chemical exchange saturation transfer MRI
Harris R, Cloughesy T, Liau L, Prins R, Antonios J, Li D, Yong W, Pope W, Lai A, Nghiemphu P, Ellingson B. pH-weighted molecular imaging of gliomas using amine chemical exchange saturation transfer MRI. Neuro-Oncology 2015, 17: 1514-1524. PMID: 26113557, PMCID: PMC4648305, DOI: 10.1093/neuonc/nov106.Peer-Reviewed Original ResearchConceptsAmine chemical exchange saturation transferPH-weighted MRIShorter time to progressionAcid lesionsTime to progressionChemical exchange saturation transfer MRIMolecular imaging of gliomaIntracranial glioma modelBrain tumor physiologyImaging of gliomasActive tumorAbnormal perfusionGlioma modelPerfusion abnormalitiesGlioblastoma patientsMolecular imaging techniquesPET uptakeTumor physiologyMR spectroscopyTissue acidosisChemical exchange saturation transferHuman patientsPatientsTumorLesionsDendritic cell immunotherapy for brain tumors
Antonios J, Everson R, Liau L. Dendritic cell immunotherapy for brain tumors. Journal Of Neuro-Oncology 2015, 123: 425-432. PMID: 26037466, DOI: 10.1007/s11060-015-1830-1.Peer-Reviewed Original ResearchConceptsDendritic cellsPatient-derived dendritic cellsDestruction of malignant cellsDendritic cell immunotherapyGlioma treatmentPre-clinical modelsCell immunotherapyDC vaccinesTreatment of gliomaActive immunotherapyProlonged survivalMalignant cellsImmunological targetsPatient-specific treatmentClinical trialsImmune responseTherapeutic approachesBrain tumorsBrain parenchymaGliomaImmunotherapyTreatmentBrainCellsImmunosuppression