2012
Immune modulation of effector CD4+ and regulatory T cell function by sorafenib in patients with hepatocellular carcinoma
Cabrera R, Ararat M, Xu Y, Brusko T, Wasserfall C, Atkinson M, Chang L, Liu C, Nelson D. Immune modulation of effector CD4+ and regulatory T cell function by sorafenib in patients with hepatocellular carcinoma. Cancer Immunology, Immunotherapy 2012, 62: 737-746. PMID: 23223899, PMCID: PMC3863727, DOI: 10.1007/s00262-012-1380-8.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsCarcinoma, HepatocellularCase-Control StudiesCD4-Positive T-LymphocytesCoculture TechniquesCytokinesDose-Response Relationship, ImmunologicEnzyme-Linked Immunosorbent AssayHumansInterleukin-2 Receptor alpha SubunitLiver NeoplasmsNiacinamidePhenylurea CompoundsSorafenibT-Lymphocytes, RegulatoryConceptsEffect of sorafenibHepatocellular carcinomaTeff activationT cellsLow dosesTeff responsesTumor immunityRegulatory T cell functionImpact of sorafenibEffector T cellsRegulatory T cellsTreg suppressive functionPeripheral mononuclear cellsCD25 surface expressionT cell functionNovel combination treatmentTreg suppressionEffector CD4Treg functionPharmacologic dosesTeff proliferationImmune reactivitySystemic drugsCD25 expressionMononuclear cells
2010
A Crucial Role for Host APCs in the Induction of Donor CD4+CD25+ Regulatory T Cell-Mediated Suppression of Experimental Graft-versus-Host Disease
Tawara I, Shlomchik WD, Jones A, Zou W, Nieves E, Liu C, Toubai T, Duran-Struuck R, Sun Y, Clouthier SG, Evers R, Lowler KP, Levy RB, Reddy P. A Crucial Role for Host APCs in the Induction of Donor CD4+CD25+ Regulatory T Cell-Mediated Suppression of Experimental Graft-versus-Host Disease. The Journal Of Immunology 2010, 185: 3866-3872. PMID: 20810991, PMCID: PMC2981818, DOI: 10.4049/jimmunol.1001625.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationAntigen-Presenting CellsBone Marrow TransplantationCell SeparationDisease Models, AnimalFlow CytometryGraft vs Host DiseaseHistocompatibility Antigens Class IIInterleukin-2 Receptor alpha SubunitLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryConceptsSuppression of GVHDDonor T cellsHost APCsBone marrow transplantationDonor TregsT cellsHost diseaseMarrow transplantationRegulatory T cell-mediated suppressionAlloreactive donor T cellsAllogeneic bone marrow transplantationT cell-mediated suppressionInduction of donorInduction of GVHDRegulatory T cellsCell-mediated suppressionDevelopment of graftExperimental GVHDGVHD protectionTreg numbersIL-10Nonmalignant diseasesAlloantigen expressionGVHDMurine modelInfluence of Serum and Soluble CD25 (sCD25) on Regulatory and Effector T‐cell Function in Hepatocellular Carcinoma
Cabrera R, Ararat M, Eksioglu E, Cao M, Xu Y, Wasserfall C, Atkinson M, Liu C, Nelson D. Influence of Serum and Soluble CD25 (sCD25) on Regulatory and Effector T‐cell Function in Hepatocellular Carcinoma. Scandinavian Journal Of Immunology 2010, 72: 293-301. PMID: 20883314, PMCID: PMC2951624, DOI: 10.1111/j.1365-3083.2010.02427.x.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, HepatocellularCell ProliferationCells, CulturedCulture Media, Serum-FreeFlow CytometryHumansInterleukin-2 Receptor alpha SubunitLiver NeoplasmsSolubilityT-LymphocytesT-Lymphocytes, RegulatoryConceptsHepatocellular carcinomaHCC serumSerum-free mediumSoluble CD25Pg/Effector T cell responsesEffector T cell functionSerum-mediated suppressionRegulatory T cellsT cell responsesSera of patientsT cell functionHealthy control cellsNovel therapeutic targetDose-dependent fashionCD25 cell surface expressionTeff responsesTreg suppressionInfluence of serumCirrhosis patientsTeff proliferationTumor burdenCD25 expressionCell surface expressionPoor survival
2009
Hepatocellular Carcinoma Immunopathogenesis: Clinical Evidence for Global T Cell Defects and an Immunomodulatory Role for Soluble CD25 (sCD25)
Cabrera R, Ararat M, Cao M, Xu Y, Wasserfall C, Atkinson M, Liu C, Nelson D. Hepatocellular Carcinoma Immunopathogenesis: Clinical Evidence for Global T Cell Defects and an Immunomodulatory Role for Soluble CD25 (sCD25). Digestive Diseases And Sciences 2009, 55: 484-495. PMID: 19714465, PMCID: PMC3161029, DOI: 10.1007/s10620-009-0955-5.Peer-Reviewed Original ResearchConceptsT cell responsesHCC patientsHepatocellular carcinomaCell responsesTumor burdenImpaired T cell responsesLower IFN-γ productionEffector T cell responsesIL-2 receptor alpha chainATP production assaysLevels of sCD25Tolerogenic tumor environmentIFN-γ ELISPOTEffector T cellsT cell immunityT cell reactivityIFN-γ productionIL-2 supplementationT cell defectsDose-dependent mannerReceptor alpha chainIL-2 signalingSerum sCD25Soluble CD25Worse survivalGamma irradiation alters the phenotype and function of CD4+CD25+ regulatory T cells
Cao M, Cabrera R, Xu Y, Liu C, Nelson D. Gamma irradiation alters the phenotype and function of CD4+CD25+ regulatory T cells. Cell Biology International 2009, 33: 565-571. PMID: 19268553, PMCID: PMC2683182, DOI: 10.1016/j.cellbi.2009.02.007.Peer-Reviewed Original ResearchConceptsRegulatory T cellsT cellsSuppression of TregsT cell proliferationDose-dependent reductionTreg expressionTreg proliferationEffector cellsImmunologic balanceSuppressive capacityTregsGy/minDose gamma irradiationFlow cytometryThymidine incorporationUpregulated BaxCell proliferationCancer therapyHigh-dose gamma irradiationApoptosis inductionDifferent dosagesFunction changesGamma irradiationPhenotypeIrradiation alters
2008
Combined Th2 cytokine deficiency in donor T cells aggravates experimental acute graft-vs-host disease
Tawara I, Maeda Y, Sun Y, Lowler K, Liu C, Toubai T, McKenzie A, Reddy P. Combined Th2 cytokine deficiency in donor T cells aggravates experimental acute graft-vs-host disease. Experimental Hematology 2008, 36: 988-996. PMID: 18410989, PMCID: PMC2603625, DOI: 10.1016/j.exphem.2008.02.010.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsBone Marrow TransplantationCD4-Positive T-LymphocytesCell ProliferationDisease Models, AnimalEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryGraft vs Host DiseaseImmunologic TestsInterleukin-2 Receptor alpha SubunitInterleukinsMajor Histocompatibility ComplexMiceMice, Inbred BALB CMice, Inbred C57BLSurvival RateTh2 CellsT-LymphocytesTransplantation, HomologousConceptsDonor T cellsT cellsWT T cellsTh2 cytokinesAcute graftAllogeneic bone marrow transplantationAllogeneic antigen-presenting cellsT cell proliferative responsesAnti-CD3 monoclonal antibodyEnhanced T cell proliferationExperimental acute graftNumber of immunoregulatoryTarget organ damageTh2 cytokine secretionBone marrow transplantationT helper 1Antigen-presenting cellsWild-type T cellsT cell proliferationGreater clinical severityBALB/cB6 recipientsGVHD mortalityHost diseaseIL-17
2007
Hepatocellular carcinoma cell supernatants increase expansion and function of CD4+CD25+ regulatory T cells
Cao M, Cabrera R, Xu Y, Firpi R, Zhu H, Liu C, Nelson D. Hepatocellular carcinoma cell supernatants increase expansion and function of CD4+CD25+ regulatory T cells. Laboratory Investigation 2007, 87: 582-590. PMID: 17372588, DOI: 10.1038/labinvest.3700540.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsRegulatory T cellsT cell proliferationT cellsCancer patientsControl peripheral blood mononuclear cellsDepletion of TregsAntigen-reactive lymphocytesTumor-related factorsBlood mononuclear cellsHepatocellular carcinoma patientsT cell populationsHost immune systemCell linesSuppressor abilityHCC cell linesHuman hepatoma cell lineAntitumor immunityCarcinoma patientsTumor burdenFoxp3 expressionMononuclear cellsCTLA-4Reactive lymphocytesTregs