2020
Kras mutation correlating with circulating regulatory T cells predicts the prognosis of advanced pancreatic cancer patients
Cheng H, Luo G, Jin K, Fan Z, Huang Q, Gong Y, Xu J, Yu X, Liu C. Kras mutation correlating with circulating regulatory T cells predicts the prognosis of advanced pancreatic cancer patients. Cancer Medicine 2020, 9: 2153-2159. PMID: 32017404, PMCID: PMC7064028, DOI: 10.1002/cam4.2895.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBiomarkers, TumorCD4 Lymphocyte CountCirculating Tumor DNADNA Mutational AnalysisFemaleFollow-Up StudiesHumansKaplan-Meier EstimateMaleMiddle AgedMutationNeoplasm StagingPancreatic NeoplasmsPolymerase Chain ReactionPrognosisProto-Oncogene Proteins p21(ras)Retrospective StudiesTime FactorsT-Lymphocytes, RegulatoryConceptsCell-free circulating tumor DNAAdvanced pancreatic cancer patientsPancreatic cancer patientsCirculating regulatory T cellsCirculating T-cell subsetsCA19-9 levelsRegulatory T cellsKRAS mutation statusT cell subsetsTumor-node-metastasisCancer patientsMutation statusTumor DNAKRAS mutationsT cellsAssociated with extremely poor survivalRegulatory T cell levelsAdvanced pancreatic cancerLevels of TregsProportion of TregsAbnormal immune statusCirculating tumor DNAT cell levelsPredicted worse prognosisTumor-node-metastasis stage
2014
A Small-Molecule c-Rel Inhibitor Reduces Alloactivation of T Cells without Compromising Antitumor Activity
Shono Y, Tuckett A, Ouk S, Liou H, Altan-Bonnet G, Tsai J, Oyler J, Smith O, West M, Singer N, Doubrovina E, Pankov D, Undhad C, Murphy G, Lezcano C, Liu C, O'Reilly R, van den Brink M, Zakrzewski J. A Small-Molecule c-Rel Inhibitor Reduces Alloactivation of T Cells without Compromising Antitumor Activity. Cancer Discovery 2014, 4: 578-591. PMID: 24550032, PMCID: PMC4011979, DOI: 10.1158/2159-8290.cd-13-0585.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFemaleGene Expression RegulationGraft vs Host DiseaseGraft vs Tumor EffectHematopoietic Stem Cell TransplantationHumansLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLProto-Oncogene Proteins c-relReceptors, Antigen, T-CellSmall Molecule LibrariesT-LymphocytesTransplantation, HomologousConceptsT cellsC-Rel activityAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationEffector T cellsRegulatory T cellsIL-2 levelsStem cell transplantationAntigen-specific cytotoxicityC-Rel-deficient T cellsC-RelHuman T cellsT cell receptor activationGut homingGVT activityImmunomodulatory therapyInhibitor administrationCell transplantationTumor activityImmune systemReceptor activationPharmaceutical inhibitionSmall molecule-based inhibitionAlloactivationBroad suppression
2013
c‐Rel is an essential transcription factor for the development of acute graft‐versus‐host disease in mice
Yu Y, Wang D, Kaosaard K, Liu C, Fu J, Haarberg K, Anasetti C, Beg A, Yu X. c‐Rel is an essential transcription factor for the development of acute graft‐versus‐host disease in mice. European Journal Of Immunology 2013, 43: 2327-2337. PMID: 23716202, PMCID: PMC3940138, DOI: 10.1002/eji.201243282.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow TransplantationCell DifferentiationCell ProliferationForkhead Transcription FactorsGraft vs Host DiseaseImmune ToleranceLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutProto-Oncogene Proteins c-relTh1 CellsTh17 CellsT-Lymphocytes, RegulatoryTransplantation, HomologousConceptsT cellsAcute GVHDHost diseaseAllogeneic bone marrow transplantationAllogeneic hematopoietic cell transplantationC-RelGVHD target organsHematopoietic cell transplantationRegulatory T cellsBone marrow transplantationAcute graftLeukemia responseTransplant toleranceAllogeneic recipientsMarrow transplantationMinor histocompatibilityCell transplantationTh1 cellsLymphoid organsMurine modelTarget organsTherapeutic interventionsNF-κB familyGraftPotential target
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 cellsRepertoire Enhancement with Adoptively Transferred Female Lymphocytes Controls the Growth of Pre-Implanted Murine Prostate Cancer
Jenq R, Curran M, Goldberg G, Liu C, Allison J, van den Brink M. Repertoire Enhancement with Adoptively Transferred Female Lymphocytes Controls the Growth of Pre-Implanted Murine Prostate Cancer. PLOS ONE 2012, 7: e35222. PMID: 22493742, PMCID: PMC3320876, DOI: 10.1371/journal.pone.0035222.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAnimalsAntigens, NeoplasmCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDEAD-box RNA HelicasesFemaleGraft vs Host DiseaseHumansImmunotherapy, AdoptiveLymphocyte CountMaleMiceMinor Histocompatibility AntigensNeoplasm TransplantationProstatic NeoplasmsSex FactorsWhole-Body IrradiationConceptsCD4 T cellsT cellsProstatic adenocarcinoma cellsAdoptive transferProstate cancerEffective anti-tumor immune responseCancer-reactive T cellsCD8 T cell responsesHigh-affinity T cellsPotential tumor rejection antigensTRAMP-C2 tumor cellsAnti-tumor immune responseAdenocarcinoma cellsExacerbation of graftPresence of CD25Female lymphocytesRegulatory T cellsAdoptive transfer modelReactive T cellsT cell responsesT cell repertoireMurine prostate cancerProstate cancer antigenAdult male hostsTumor rejection antigens
2011
Abrogation of donor T-cell IL-21 signaling leads to tissue-specific modulation of immunity and separation of GVHD from GVL
Hanash A, Kappel L, Yim N, Nejat R, Goldberg G, Smith O, Rao U, Dykstra L, Na I, Holland A, Dudakov J, Liu C, Murphy G, Leonard W, Heller G, van den Brink M. Abrogation of donor T-cell IL-21 signaling leads to tissue-specific modulation of immunity and separation of GVHD from GVL. Blood 2011, 118: 446-455. PMID: 21596854, PMCID: PMC3138694, DOI: 10.1182/blood-2010-07-294785.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGene Knockdown TechniquesGraft vs Host DiseaseGraft vs Leukemia EffectHumansImmunity, InnateInterleukin-21 Receptor alpha SubunitInterleukinsLymphocytes, Tumor-InfiltratingMiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred DBAMice, KnockoutOrgan SpecificitySignal TransductionTissue DonorsT-LymphocytesTransplantation ImmunologyConceptsSeparation of GVHDDonor T cellsKO T cellsIL-21T cellsTissue-specific modulationGastrointestinal GVHDCytokine productionWild-type donor T cellsDonor regulatory T cellsTh cell cytokine productionPeripheral T cell functionMesenteric lymph nodesRegulatory T cellsTh cell functionIL-21 signalingInflammatory cytokine productionBM transplantation modelT cell functionLymphoma responseLymph nodesProinflammatory cytokinesTransplantation outcomesTransplantation modelGVHDKinase inhibitor Sorafenib modulates immunosuppressive cell populations in a murine liver cancer model
Cao M, Xu Y, Youn J, Cabrera R, Zhang X, Gabrilovich D, Nelson D, Liu C. Kinase inhibitor Sorafenib modulates immunosuppressive cell populations in a murine liver cancer model. Laboratory Investigation 2011, 91: 598-608. PMID: 21321535, PMCID: PMC3711234, DOI: 10.1038/labinvest.2010.205.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzenesulfonatesBone Marrow CellsCarcinoma, HepatocellularCell DivisionCell Line, TumorDisease ProgressionImmunity, CellularLiver NeoplasmsMiceMice, Inbred BALB CMyeloid CellsNiacinamidePhenylurea CompoundsProtein Kinase InhibitorsPyridinesSorafenibSpleenT-Lymphocytes, RegulatoryConceptsMyeloid-derived suppressor cellsImmunosuppressive cell populationsAnti-tumor immunityTumor-bearing hostsImmune cell populationsLiver cancer modelMurine liver cancer modelHepatocellular carcinomaCell populationsCancer modelNovel multi-kinase inhibitorSuppressive immune cell populationBALB/c miceDepletion of TregsImpact of sorafenibRegulatory T cellsAdvanced hepatocellular carcinomaTreatment of sorafenibKinase inhibitor sorafenibMulti-kinase inhibitorHCC cell growthSuppressor cellsTumor burdenC miceCancer patientsInterleukin-6 Modulates Graft-versus-Host Responses after Experimental Allogeneic Bone Marrow Transplantation
Tawara I, Koyama M, Liu C, Toubai T, Thomas D, Evers R, Chockley P, Nieves E, Sun Y, Lowler K, Malter C, Nishimoto N, Hill G, Reddy P. Interleukin-6 Modulates Graft-versus-Host Responses after Experimental Allogeneic Bone Marrow Transplantation. Clinical Cancer Research 2011, 17: 77-88. PMID: 21047980, PMCID: PMC3058832, DOI: 10.1158/1078-0432.ccr-10-1198.Peer-Reviewed Original ResearchConceptsAllogeneic bone marrow transplantationBone marrow transplantationDonor T cellsIL-6 deficiencyInterleukin-6MR16-1T cellsMarrow transplantationExperimental allogeneic bone marrow transplantationDonor regulatory T cellsBeneficial GVT effectsMR16-1 treatmentRegulatory T cellsProlongation of survivalDonor bone marrowEffector cell expansionRelevant murine modelIL-6 receptorBMT patientsGVT responseGVT effectHost diseaseBMT recipientsMAb therapyTumor effect
2010
Different radiosensitivity of CD4+CD25+ regulatory T cells and effector T cells to low dose gamma irradiation in vitro
Cao M, Cabrera R, Xu Y, Liu C, Nelson D. Different radiosensitivity of CD4+CD25+ regulatory T cells and effector T cells to low dose gamma irradiation in vitro. International Journal Of Radiation Biology 2010, 87: 71-80. PMID: 20958220, PMCID: PMC3806980, DOI: 10.3109/09553002.2010.518208.Peer-Reviewed Original ResearchMeSH KeywordsAgedApoptosisBcl-2-Associated X ProteinCarcinoma, HepatocellularCaspase 3Cell ProliferationDose-Response Relationship, RadiationFas ReceptorFemaleGamma RaysHumansIn Vitro TechniquesInterferon-gammaInterleukin-10Liver NeoplasmsMaleMiddle AgedRadiation ToleranceT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryConceptsEffector T cellsAdvanced hepatocellular carcinomaRegulatory T cellsT cellsHepatocellular carcinomaLow-dose gamma raysLow-dose irradiationApoptosis-related proteinsImmune responseLow dosesEnhanced immune responseCaspase-3Dose-dependent reductionB-cell lymphoma 2X protein expressionCell lymphoma 2Interleukin-10Peripheral bloodActive caspase-3Low-dose gamma irradiationCytokine secretionTregsLuminex assaysBlood samplesInduction of apoptosisA 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 ResearchConceptsHepatocellular 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
A Crucial Role for Antigen Presenting Cells in Donor CD4+CD25+ Regulatory T Cell Mediated Suppression of Experimental Gvhd.
Tawara I, Toubai T, Malter C, Sun Y, Nieves E, Lowler K, Liu C, Ferrara J, Reddy P. A Crucial Role for Antigen Presenting Cells in Donor CD4+CD25+ Regulatory T Cell Mediated Suppression of Experimental Gvhd. Blood 2009, 114: 688. DOI: 10.1182/blood.v114.22.688.688.Peer-Reviewed Original ResearchHost antigen presenting cellsAntigen presenting cellsGVHD mortalityGVHD protectionT cellsWT recipientsIL-10Effector phaseDonor TregsExperimental GVHDAllo-antigenB6 animalsPresenting cellsClass IIProfessional antigen presenting cellsLack of TregsMaintenance of GVHDRegulation of GVHDResponse of TregsExpansion of CD8Target tissuesRegulatory T cellsT cell effectorsClass II expressionHost target tissuesGamma 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
Extracorporeal photopheresis reverses experimental graft-versus-host disease through regulatory T cells
Gatza E, Rogers C, Clouthier S, Lowler K, Tawara I, Liu C, Reddy P, Ferrara J. Extracorporeal photopheresis reverses experimental graft-versus-host disease through regulatory T cells. Blood 2008, 112: 1515-1521. PMID: 18411417, PMCID: PMC2515148, DOI: 10.1182/blood-2007-11-125542.Peer-Reviewed Original ResearchConceptsRegulatory T cellsExtracorporeal photopheresisHost diseaseT cellsDonor regulatory T cellsCutaneous T-cell lymphomaOngoing immune responseImmune-mediated diseasesT-cell lymphomaRelevant murine modelWhite blood cellsImmune responseMurine modelLymphocyte apoptosisImmune systemExperimental graftBlood cellsDiseaseECP treatmentGVHDPhotopheresisGraftDirect inductionCellsApoptosis
2007
CEACAM-1 Is Involved in Graft-Versus-Host-Disease in Murine Allogeneic Bone Marrow Transplantation Models.
Lu S, Willis L, Smith M, Suh D, King C, Bautista J, Chow M, Cabrera-Perez J, Hubbard V, Rotolo J, Liu C, Murphy G, Alpdogan O, Blumberg R, Holmes K, Turbide C, Beauchemin N, van den Brink M. CEACAM-1 Is Involved in Graft-Versus-Host-Disease in Murine Allogeneic Bone Marrow Transplantation Models. Blood 2007, 110: 67. DOI: 10.1182/blood.v110.11.67.67.Peer-Reviewed Original ResearchWT T cellsT cellsWT recipientsAdoptive transferSmall bowelMurine allogeneic bone marrow transplantation modelWT controlsAllogeneic bone marrow transplantation modelCarcinoembryonic antigenSplenic regulatory T cellsAllogeneic bone marrow transplantationCEACAM-1Cell adhesion molecule-1Conditioning-related toxicityDonor T cellsGVHD target organsPeripheral lymph nodesRegulatory T cellsAlloreactive T cellsBone marrow transplantation modelBone marrow transplantationDonor bone marrowAdhesion molecule-1T cell apoptosisT cell activationHepatocellular 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