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 system
2017
NIMG-36. DELINEATION OF IMMUNE RESPONSES AFTER IMMUNOTHERAPY IN GLIOBLASTOMA USING PET AND MRI
Soto H, Antonios J, Everson R, Moughon D, Wang A, Orpilla J, Radu C, Ellingson B, Lee J, Cloughesy T, Phelps M, Czernin J, Liau L, Prins R. NIMG-36. DELINEATION OF IMMUNE RESPONSES AFTER IMMUNOTHERAPY IN GLIOBLASTOMA USING PET AND MRI. Neuro-Oncology 2017, 19: vi149-vi150. PMCID: PMC5692246, DOI: 10.1093/neuonc/nox168.611.Peer-Reviewed Original ResearchPD-1Dendritic cellsMAb blockadeContrast enhancementHost anti-tumor immune responseTreated with dendritic cellsAnti-tumor immune responseInflammatory responseClinical management of patientsDendritic cell vaccinesTumor-infiltrating lymphocytesSyngeneic immunocompetent miceTreated with immunotherapyCo-registration of PETSecondary lymphoid organsContrast-enhanced MRIManagement of patientsProbe uptakePET probeImmune inflammatory responseNon-invasive modalityNon-invasive imaging techniqueImmunocompetent micePre-contrast T1Cell vaccineDetection 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 gliomasImmunosuppressive 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
IMST-28. NON-INVASIVE IMMUNE MONITORING FOLLOWING DC VACCINATION EFFECTIVELY DELINEATES IMMUNE RESPONSES IN GLIOBLASTOMA
Antonios J, Soto H, Everson R, Orpilla J, Shin N, Nathanson D, Harris R, Sadeghi S, Ellingson B, Liau L, Prins R. IMST-28. NON-INVASIVE IMMUNE MONITORING FOLLOWING DC VACCINATION EFFECTIVELY DELINEATES IMMUNE RESPONSES IN GLIOBLASTOMA. Neuro-Oncology 2016, 18: vi92-vi92. DOI: 10.1093/neuonc/now212.384.Peer-Reviewed Original ResearchDC vaccinesImmune monitoringFACS analysisPD-1Immune monitoring of patientsActivated tumor-infiltrating lymphocytesDC vaccine treatmentTumor-infiltrating lymphocytesImmunocompetent C57BL/6 miceMAb-treated miceTumor-bearing hemisphereGL261 glioma cellsPET signal intensityActive lymphocytic infiltrationImmunotherapy fieldMonitoring of patientsMedian survivalStandard chemotherapyClinically relevant modalityMeasures of immune responseNeedle biopsyLymphocytic infiltrationTreated miceLymphocyte responsesNon-invasiveIMST-56. TUMOR LYSATE-PULSED DC VACCINATION INDUCES NEOANTIGEN-SPECIFIC T CELL RESPONSES
Everson R, Shin N, Antonios J, Soto H, Tucker A, Zaretsky J, Orpilla J, Rathe S, Popescu F, Largaespada D, Liau L, Prins R. IMST-56. TUMOR LYSATE-PULSED DC VACCINATION INDUCES NEOANTIGEN-SPECIFIC T CELL RESPONSES. Neuro-Oncology 2016, 18: vi99-vi99. DOI: 10.1093/neuonc/now212.412.Peer-Reviewed Original ResearchAutologous tumor lysateTumor-infiltrating lymphocytesTumor-specific mutationsDC vaccinesDendritic cellsCD8+ T cell responsesEnhanced T cell infiltrationTumor-infiltrating lymphocyte culturesImmune responseIntracranial GL261 gliomasT cell infiltrationT cell responsesPhase III trialsTreatment groupsRelevant target antigensMurine glioma cell lineDC therapyTCR clonotypesTumor lysateGL261 gliomasIII trialsNeoantigen peptidesOriginal tumorGlioma cell linesLymphocytic infiltrationPD-1 blockade enhances the vaccination-induced immune response in glioma
Antonios J, Soto H, Everson R, Orpilla J, Moughon D, Shin N, Sedighim S, Yong W, Li G, Cloughesy T, Liau L, Prins R. PD-1 blockade enhances the vaccination-induced immune response in glioma. JCI Insight 2016, 1: e87059. PMID: 27453950, PMCID: PMC4951098, DOI: 10.1172/jci.insight.87059.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesPD-1 blockadeDC vaccinesPD-1/PD-L1PD-1Survival benefitMAb blockadeProgrammed death-1/programmed death-ligand 1Effect of PD-1 blockadeBlockade of PD-1Induced T cell infiltrationIsolated tumor-infiltrating lymphocytesPD-1 pathway inhibitionActive vaccinationCD8<sup>+</sup> T cellsPD-1/PD-L1 pathwayImmune responseVaccination-induced immune responsesAutologous tumor lysateIntratumoral immune responseNegative costimulatory pathwaysAdaptive immune resistanceDeath-ligand 1T cell infiltrationTumor cell cytolysisTCR 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
2014
IT-01PD1/PDL1 INTERACTIONS MEDIATE SUPPRESSION OF ANTI-TUMOR IMMUNE ACTIVITY IN GLIOMA
Antonios J, Soto H, Harris R, Nathanson D, Sadeghi S, Ellingson B, Liau L, Prins R. IT-01PD1/PDL1 INTERACTIONS MEDIATE SUPPRESSION OF ANTI-TUMOR IMMUNE ACTIVITY IN GLIOMA. Neuro-Oncology 2014, 16: v110-v110. PMCID: PMC4218227, DOI: 10.1093/neuonc/nou258.1.Peer-Reviewed Original ResearchProgrammed death-1Tumor-infiltrating lymphocytesPost-implant dayCombination groupPD-1Tumor microenvironmentLymph nodesTreatment groupsEffective anti-tumor immune responseFACS analysisAnti-tumor immune activityAnti-tumor immune responseIncreased tumor-infiltrating lymphocytesAnti-PD1 mAbNegative costimulatory moleculesPD-1 mAbDendritic cell vaccinesAnti-tumor responsesImmunocompetent C57BL/6 miceTumor-bearing hemisphereDecreased tumor volumeGL261 glioma cellsCombined treatment groupAntitumor responseDeath-1