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 surfaceTemozolomide lymphodepletion enhances CAR abundance and correlates with antitumor efficacy against established glioblastoma
Suryadevara CM, Desai R, Abel ML, Riccione KA, Batich KA, Shen SH, Chongsathidkiet P, Gedeon PC, Elsamadicy AA, Snyder DJ, Herndon JE, Healy P, Archer GE, Choi BD, Fecci PE, Sampson JH, Sanchez-Perez L. Temozolomide lymphodepletion enhances CAR abundance and correlates with antitumor efficacy against established glioblastoma. OncoImmunology 2018, 7: e1434464. PMID: 29872570, PMCID: PMC5980382, DOI: 10.1080/2162402x.2018.1434464.Peer-Reviewed Original ResearchChimeric antigen receptorMurine modelAntitumor efficacyFirst-line chemotherapyPhase I trialLong-term survivorsMajor side effectsB-cell malignanciesCAR immunotherapyCare temozolomideHost lymphodepletionLine chemotherapyAdoptive transferEffective immunotherapyI trialComplete regressionStandard treatmentIntracerebral tumorsSimilar efficacyTreatment strategiesT cellsGBM patientsBrain tumorsSide effectsOrthotopic glioma