2015
Targeting Host Complement C3a/C5a Receptors to Control of Acute Graft-Versus-Host Disease in Mice
Nguyen H, Heinrichs J, Fu J, Wu Y, Bastian D, Schutt S, Daenthanasanmak A, Dany M, Liu C, Fairlie D, Tomlinson S, Yu X. Targeting Host Complement C3a/C5a Receptors to Control of Acute Graft-Versus-Host Disease in Mice. Blood 2015, 126: 3076. DOI: 10.1182/blood.v126.23.3076.3076.Peer-Reviewed Original ResearchC3aR/C5aRAntigen presenting cellsDonor T cellsT cellsGVL activityHost diseaseC5aR signalingAlloreactive donor T cellsDonor T cell activationDonor T-cell responsesHost antigen presenting cellsAllogeneic hematopoietic cell transplantationComplement systemAcute Graft-VersusControl of GVHDHost hematopoietic cellsDevelopment of GVHDGVHD target organsAdaptive immune cellsHematopoietic cell transplantationEffector T cellsT cell responsesTotal body irradiationAlloreactive T cellsPro-inflammatory cytokinesHuman 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 disruptionRORγt
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 GVHDCCR1/CCL5 (RANTES) receptor-ligand interactions modulate allogeneic T-cell responses and graft-versus-host disease following stem-cell transplantation
Choi S, Hildebrandt G, Olkiewicz K, Hanauer D, Chaudhary M, Silva I, Rogers C, Deurloo D, Fisher J, Liu C, Adams D, Chensue S, Cooke K. CCR1/CCL5 (RANTES) receptor-ligand interactions modulate allogeneic T-cell responses and graft-versus-host disease following stem-cell transplantation. Blood 2007, 110: 3447-3455. PMID: 17641205, PMCID: PMC2200916, DOI: 10.1182/blood-2007-05-087403.Peer-Reviewed Original ResearchConceptsStem cell transplantationT cell responsesCCR1 expressionHost diseaseT cellsAllogeneic T-cell responsesAllogeneic stem cell transplantationCCR1-deficient miceDevelopment of GVHDCytolytic effector functionDonor cellsT cell functionChemokine receptor-ligand interactionsT cell proliferationHost target tissuesReceptor-ligand interactionsActivated T cellsAcute graftGVHD mortalityGVL activityIFNgamma secretionAllo-SCTGVHD severityLeukemic infiltrationLeukemic relapse
2005
Absence of inducible costimulator on alloreactive T cells reduces graft versus host disease and induces Th2 deviation
Hubbard V, Eng J, Ramirez-Montagut T, Tjoe K, Muriglan S, Kochman A, Terwey T, Willis L, Schiro R, Heller G, Murphy G, Liu C, Alpdogan O, van den Brink M. Absence of inducible costimulator on alloreactive T cells reduces graft versus host disease and induces Th2 deviation. Blood 2005, 106: 3285-3292. PMID: 15956289, PMCID: PMC1895338, DOI: 10.1182/blood-2005-01-0410.Peer-Reviewed Original ResearchConceptsAlloreactive T cellsInducible costimulatorT cellsHost diseaseInterleukin-4Allogeneic hematopoietic stem cell transplantationRole of ICOSHematopoietic stem cell transplantationLess GVHD morbidityTh2 immune deviationIL-10 levelsTh1/Th2 developmentMemory T cellsStem cell transplantationWild-type T cellsActivated T cellsCutaneous GVHDGVHD morbidityGVL activityHepatic GVHDImmune deviationLess GVHDTh2 deviationGVHD modelT helper
2004
Histone deacetylase inhibitor suberoylanilide hydroxamic acid reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect
Reddy P, Maeda Y, Hotary K, Liu C, Reznikov L, Dinarello C, Ferrara J. Histone deacetylase inhibitor suberoylanilide hydroxamic acid reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 3921-3926. PMID: 15001702, PMCID: PMC374345, DOI: 10.1073/pnas.0400380101.Peer-Reviewed Original ResearchConceptsBone marrow transplantationSuberoylanilide hydroxamic acidAdministration of SAHAProinflammatory cytokinesGVL activityAcute graftHost diseaseHost antigensTime of BMTAllogeneic bone marrow transplantationDonor/recipient combinationsEffects of SAHACytotoxic T cell responsesCytotoxic responseBeneficial GVL effectLeukemia-free survivalT cell proliferativeHistone deacetylase inhibitor suberoylanilide hydroxamic acidT cell responsesVehicle-treated animalsGastrointestinal tract integrityInhibitor suberoylanilide hydroxamic acidHistone deacetylase inhibitionAcute GVHDGVL effect