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
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 systemImmunosuppressive 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
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
2015
pH-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 patientsPatientsTumorLesions