2019
SPINT2 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 consequences
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