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
Immunosuppressive 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
TMIC-16. TUMOR-INFILTRATING MYELOID CELLS MEDIATE ADAPTIVE IMMUNE RESISTANCE IN GLIOBLASTOMA
Antonios J, Soto H, Everson R, Orpilla J, Shin N, Moughon D, Sedighim S, Treger J, Odesa S, Tucker A, Yong W, Cloughesy T, Prins R, Liau L. TMIC-16. TUMOR-INFILTRATING MYELOID CELLS MEDIATE ADAPTIVE IMMUNE RESISTANCE IN GLIOBLASTOMA. Neuro-Oncology 2016, 18: vi203-vi203. DOI: 10.1093/neuonc/now212.856.Peer-Reviewed Original ResearchPD-1 mAbPD-1/PD-L1PD-1Immune responseDendritic cellsMAb blockadeColony stimulating factor 1 receptor inhibitorTumor lysate-pulsed dendritic cellsProgrammed death-1/ligand-1Cytolysis of tumor cellsMurine in vivo studiesDC vaccine treatmentAdaptive immune resistanceExpressed PD-L1Cell populationsVaccine treatmentTreatment to miceDominant mediatorIn vitro cytotoxicity assayTIL populationsPD-L1TIL infiltrationGL261 tumorsReceptor inhibitorsTumor microenvironmentPD-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 cytolysis