2015
Human Mesenchymal Stromal Cells Attenuate Graft‐Versus‐Host Disease and Maintain Graft‐Versus‐Leukemia Activity Following Experimental Allogeneic Bone Marrow Transplantation
Auletta J, Eid S, Wuttisarnwattana P, Silva I, Metheny L, Keller M, Guardia‐Wolff R, Liu C, Wang F, Bowen T, Lee Z, Solchaga L, Ganguly S, Tyler M, Wilson D, Cooke K. Human Mesenchymal Stromal Cells Attenuate Graft‐Versus‐Host Disease and Maintain Graft‐Versus‐Leukemia Activity Following Experimental Allogeneic Bone Marrow Transplantation. Stem Cells 2015, 33: 601-614. PMID: 25336340, PMCID: PMC4304927, DOI: 10.1002/stem.1867.Peer-Reviewed Original ResearchConceptsT cell expansionT cell proliferationGraft-VersusHost diseaseLeukemia activityExperimental allogeneic bone marrow transplantationDonor T cell expansionAllogeneic bone marrow transplantationCytotoxic T cell activityAlloreactive T cell proliferationPotent GVL effectCyclo-oxygenase inhibitionT cell activityT cell suppressionBone marrow transplantationMarrow-derived mesenchymal stromal cellsSecondary lymphoid organsSplenic T cellsSplenic marginal zoneMixed leukocyte cultureMesenchymal stromal cellsBMT miceEP2 agonismGVL activityGVL effect
2013
Pharmacologic inhibition of PKCα and PKCθ prevents GVHD while preserving GVL activity in mice
Haarberg K, Li J, Heinrichs J, Wang D, Liu C, Bronk C, Kaosaard K, Owyang A, Holland S, Masuda E, Tso K, Blazar B, Anasetti C, Beg A, Yu X. Pharmacologic inhibition of PKCα and PKCθ prevents GVHD while preserving GVL activity in mice. Blood 2013, 122: 2500-2511. PMID: 23908466, PMCID: PMC3790515, DOI: 10.1182/blood-2012-12-471938.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell SeparationDisease Models, AnimalEnzyme InhibitorsFlow CytometryGraft vs Host DiseaseGraft vs Leukemia EffectHematopoietic Stem Cell TransplantationIsoenzymesLeukemiaLymphocyte ActivationLymphomaMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutProtein Kinase CProtein Kinase C-alphaProtein Kinase C-thetaT-LymphocytesConceptsHematopoietic cell transplantationDonor T cell proliferationAllogeneic hematopoietic cell transplantationT cell proliferationGVL activityGVL effectCytokine productionT cellsPharmacologic inhibitionChemokine/cytokine productionT-cell cytotoxicDonor T cellsPreclinical murine modelsPotential therapeutic targetT cell activationGVHD inductionGVHD preventionPrevents GVHDHost diseaseLeukemia effectSevere graftTherapeutic optionsCell transplantationEffective therapyPharmacologic approaches
2011
Prevention of GVHD while sparing GVL effect by targeting Th1 and Th17 transcription factor T-bet and RORγt in mice
Yu Y, Wang D, Liu C, Kaosaard K, Semple K, Anasetti C, Yu X. Prevention of GVHD while sparing GVL effect by targeting Th1 and Th17 transcription factor T-bet and RORγt in mice. Blood 2011, 118: 5011-5020. PMID: 21856864, PMCID: PMC3208306, DOI: 10.1182/blood-2011-03-340315.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCells, CulturedCombined Modality TherapyGraft vs Host DiseaseGraft vs Leukemia EffectHematopoietic Stem Cell TransplantationLeukemiaMiceMice, Inbred C57BLMice, KnockoutMolecular Targeted TherapyNuclear Receptor Subfamily 1, Group F, Member 3T-Box Domain ProteinsTh1 CellsTh17 CellsTransplantation, HomologousConceptsHematopoietic cell transplantationGVL effectT-betT cellsTranscription factor T-betPrevention of GVHDDonor T cellsCD8 T cellsAmeliorated GVHDGVL activityNaive ThTh17 subsetAdoptive transferCell transplantationTh17 differentiationEffective therapyHematologic malignanciesAllogeneic hostsGVHDMajor MHCTh1Regulatory phenotypeSkewed differentiationTargeted disruptionRORγtAbrogation 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 modelGVHD
2007
β2 integrins separate graft-versus-host disease and graft-versus-leukemia effects
Liang Y, Liu C, Djeu J, Zhong B, Peters T, Scharffetter-Kochanek K, Anasetti C, Yu X. β2 integrins separate graft-versus-host disease and graft-versus-leukemia effects. Blood 2007, 111: 954-962. PMID: 17928532, PMCID: PMC2200850, DOI: 10.1182/blood-2007-05-089573.Peer-Reviewed Original ResearchConceptsT cellsHost diseaseLeukemia effectMurine allogeneic bone marrow transplantation modelAllogeneic bone marrow transplantation modelWild-type donor T cellsAllogeneic hematopoietic stem cell transplantationDonor T-cell infiltrationDonor-derived T cellsHematopoietic stem cell transplantationBeta2 integrinsAnalysis of alloreactivityLess GVHD morbidityDevelopment of GVHDDonor T cellsGVHD target organsT cell infiltrationBone marrow transplantation modelStem cell transplantationWT T cellsT cell activationGVHD morbidityGVL activityGVL effectLess GVHD
2005
A crucial role for antigen-presenting cells and alloantigen expression in graft-versus-leukemia responses
Reddy P, Maeda Y, Liu C, Krijanovski O, Korngold R, Ferrara J. A crucial role for antigen-presenting cells and alloantigen expression in graft-versus-leukemia responses. Nature Medicine 2005, 11: 1244-1249. PMID: 16227991, DOI: 10.1038/nm1309.Peer-Reviewed Original ResearchConceptsBone marrow transplantationAllogeneic bone marrow transplantationGVL responseLeukemia responseAlloantigen expressionInduction of graftAntigen-presenting cellsHost diseaseSerious complicationsDonor APCsMarrow transplantationTumor burdenTumor modelGraftAPCHost originPotent formResponseImmunotherapyCellsComplicationsTransplantationAcuityExpressionTumors
2003
Repifermin (keratinocyte growth factor-2) reduces the severity of graft-versus-host disease while preserving a graft-versus-leukemia effect
Clouthier S, Cooke K, Teshima T, Lowler K, Liu C, Connolly K, Ferrara J. Repifermin (keratinocyte growth factor-2) reduces the severity of graft-versus-host disease while preserving a graft-versus-leukemia effect. Transplantation And Cellular Therapy 2003, 9: 592-603. PMID: 14506661, DOI: 10.1016/s1083-8791(03)00230-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow TransplantationCD4 Lymphocyte CountCD8-Positive T-LymphocytesCell DivisionCell Line, TumorDisease Models, AnimalFemaleFibroblast Growth Factor 10Fibroblast Growth FactorsGraft vs Host DiseaseGraft vs Leukemia EffectHumansInterferon-gammaInterleukin-2IntestinesLipopolysaccharidesLiverLymphocyte CountMiceMice, Inbred C57BLMice, Inbred StrainsRecombinant ProteinsSpleenT-LymphocytesT-Lymphocytes, CytotoxicTransplantation, HomologousTumor Necrosis Factor-alphaConceptsBone marrow transplantationAllogeneic bone marrow transplantationAllogeneic BMT recipientsSystemic GVHDGVL effectHost diseaseBMT recipientsTumor necrosis factor alphaBeneficial GVL effectInduction of GVHDSeverity of graftToxicity of GVHDMurine BMT modelBone marrow inoculumNecrosis factor alphaT cell proliferationRecombinant human keratinocyte growth factorHuman keratinocyte growth factorKeratinocyte growth factorLeukemia effectLeukemia responseSerum levelsMarrow transplantationControl miceOrgan histopathology
2002
Pretreatment of donors with interleukin-18 attenuates acute graft-versus-host disease via STAT6 and preserves graft-versus-leukemia effects
Reddy P, Teshima T, Hildebrandt G, Williams D, Liu C, Cooke K, Ferrara J. Pretreatment of donors with interleukin-18 attenuates acute graft-versus-host disease via STAT6 and preserves graft-versus-leukemia effects. Blood 2002, 101: 2877-2885. PMID: 12433681, DOI: 10.1182/blood-2002-08-2566.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsBone Marrow TransplantationFemaleGraft vs Host DiseaseGraft vs Leukemia EffectHumansInterferon-gammaInterleukin-18Leukemia, ExperimentalMiceMice, Inbred BALB CMice, Inbred C57BLSTAT6 Transcription FactorSurvival RateT-LymphocytesTissue DonorsTrans-ActivatorsTransplantation, HomologousConceptsAllogeneic bone marrow transplantationBone marrow transplantationPretreatment of donorsIL-18Acute GVHDAcute graftHost diseaseLeukemia effectTransplant donorsCytotoxic T lymphocyte activityAcute GVHD mortalityIL-18 pretreatmentDonor T cellsT lymphocyte activityBM transplant recipientsIL-4 secretionSTAT6-dependent mechanismIL-18 treatmentGVHD mortalityGVL effectPreserves graftTransplant recipientsInterleukin-18Marrow transplantationBM donors