2018
T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma
Woroniecka K, Chongsathidkiet P, Rhodin K, Kemeny H, Dechant C, Farber SH, Elsamadicy AA, Cui X, Koyama S, Jackson C, Hansen LJ, Johanns TM, Sanchez-Perez L, Chandramohan V, Yu YA, Bigner DD, Giles A, Healy P, Dranoff G, Weinhold KJ, Dunn GP, Fecci PE. T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma. Clinical Cancer Research 2018, 24: 4175-4186. PMID: 29437767, PMCID: PMC6081269, DOI: 10.1158/1078-0432.ccr-17-1846.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsCD8-Positive T-LymphocytesFemaleFlow CytometryGene Expression Regulation, NeoplasticGlioblastomaHumansInterferon-gammaInterleukin-2Lymphocytes, Tumor-InfiltratingMaleMiceMiddle AgedReceptors, Antigen, T-Cell, alpha-betaT-LymphocytesTumor MicroenvironmentTumor Necrosis Factor-alphaConceptsT cell dysfunctionMultiple immune checkpointsT cellsExhaustion signaturesImmune checkpointsT cell exhaustion signaturesTumor-specific T cellsEffective immunotherapeutic strategiesImmune checkpoint blockadeT cell exhaustionImmunocompetent murine modelT cell hyporesponsivenessPeripheral blood lymphocytesClin Cancer ResPoststimulation levelsCheckpoint blockadeImmunotherapeutic strategiesCytokines IFNγHallmark of glioblastomaInhibitory receptorsTIL functionTumor locationMurine glioblastomaBlood lymphocytesMurine modelSequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors
Chongsathidkiet P, Jackson C, Koyama S, Loebel F, Cui X, Farber SH, Woroniecka K, Elsamadicy AA, Dechant CA, Kemeny HR, Sanchez-Perez L, Cheema TA, Souders NC, Herndon JE, Coumans JV, Everitt JI, Nahed BV, Sampson JH, Gunn MD, Martuza RL, Dranoff G, Curry WT, Fecci PE. Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nature Medicine 2018, 24: 1459-1468. PMID: 30104766, PMCID: PMC6129206, DOI: 10.1038/s41591-018-0135-2.Peer-Reviewed Original ResearchConceptsT cell dysfunctionT cellsBone marrowCell dysfunctionT cell sequestrationTreatment-naïve subjectsT-cell lymphopeniaNaïve T cellsSetting of glioblastomaT cell surfaceCD4 countLymphoid organsImmune escapeCell lymphopeniaIntracranial tumorsCell sequestrationMurine modelIntracranial compartmentGlioblastomaMarrowDysfunctionTumorsCancerCellsCell surfaceFlow Cytometric Identification of Tumor-Infiltrating Lymphocytes from Glioblastoma
Woroniecka K, Chongsathidkiet P, Elsamadicy A, Farber H, Cui X, Fecci PE. Flow Cytometric Identification of Tumor-Infiltrating Lymphocytes from Glioblastoma. Methods In Molecular Biology 2018, 1741: 221-226. PMID: 29392704, PMCID: PMC6825407, DOI: 10.1007/978-1-4939-7659-1_18.Peer-Reviewed Original Research
2017
Prospect of rindopepimut in the treatment of glioblastoma
Elsamadicy AA, Chongsathidkiet P, Desai R, Woroniecka K, Farber SH, Fecci PE, Sampson JH. Prospect of rindopepimut in the treatment of glioblastoma. Expert Opinion On Biological Therapy 2017, 17: 507-513. PMID: 28274144, PMCID: PMC5787389, DOI: 10.1080/14712598.2017.1299705.Peer-Reviewed Original ResearchConceptsKeyhole limpet hemocyaninClinical efficacyClinical trialsEpidermal growth factor receptor variant IIIPhase III clinical trialsPhase II clinical trialPrimary malignant neoplasmsTreatment of GBMSub-group analysisTumor-specific epitopesTreatment of glioblastomaTumor-specific activityPrimary endpointClinical benefitMalignant neoplasmsPeptide vaccineInhibition of apoptosisSignificant efficacyGBM therapyRindopepimutAmino acid peptideLimpet hemocyaninVariant IIIGBM cellsEGFRvIII mutationThe Safety of available immunotherapy for the treatment of glioblastoma
Farber SH, Elsamadicy AA, Atik AF, Suryadevara CM, Chongsathidkiet P, Fecci PE, Sampson JH. The Safety of available immunotherapy for the treatment of glioblastoma. Expert Opinion On Drug Safety 2017, 16: 277-287. PMID: 27989218, PMCID: PMC5404815, DOI: 10.1080/14740338.2017.1273898.Peer-Reviewed Original ResearchConceptsClinical trialsCurrent immunotherapiesCommon malignant primary brain tumorMalignant primary brain tumorAdoptive T-cell immunotherapyReviewed clinical trialsRole of immunotherapyImmune checkpoint blockadeMaximal surgical resectionOngoing clinical trialsPrimary brain tumorsT-cell immunotherapyTreatment of glioblastomaAdjuvant chemoradiationAvailable immunotherapiesCheckpoint blockadeCytokine therapySurgical resectionImmunotherapeutic approachesCell immunotherapyPatient survivalRecurrent glioblastomaVaccination strategiesSafety dataBrain tumors