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 approachesHost-derived CD8+ dendritic cells are required for induction of optimal graft-versus-tumor responses after experimental allogeneic bone marrow transplantation
Toubai T, Sun Y, Luker G, Liu J, Luker K, Tawara I, Evers R, Liu C, Mathewson N, Malter C, Nieves E, Choi S, Murphy K, Reddy P. Host-derived CD8+ dendritic cells are required for induction of optimal graft-versus-tumor responses after experimental allogeneic bone marrow transplantation. Blood 2013, 121: 4231-4241. PMID: 23520337, PMCID: PMC3656455, DOI: 10.1182/blood-2012-05-432872.Peer-Reviewed Original ResearchConceptsAntigen-presenting cellsTumor-specific antigensGVT responseAllo-HCTAPC subsetsDendritic cellsExperimental allogeneic bone marrow transplantationHost-derived antigen-presenting cellsAllogeneic bone marrow transplantationAllogeneic hematopoietic cell transplantationAlloantigen-specific responsesHost-derived CD8Donor T cellsHematopoietic cell transplantationBone marrow transplantationRelevant murine modelStimulation of TLR3Host diseaseTumor effectMarrow transplantationCell transplantationTumor responseSerious toxicityT cellsOptimal graft
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
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
2003
LPAM (α4β7 integrin) is an important homing integrin on alloreactive T cells in the development of intestinal graft-versus-host disease
Petrovic A, Alpdogan O, Willis L, Eng J, Greenberg A, Kappel B, Liu C, Murphy G, Heller G, van den Brink M. LPAM (α4β7 integrin) is an important homing integrin on alloreactive T cells in the development of intestinal graft-versus-host disease. Blood 2003, 103: 1542-1547. PMID: 14563643, DOI: 10.1182/blood-2003-03-0957.Peer-Reviewed Original ResearchConceptsDonor T cellsT cellsMurine allogeneic bone marrow transplantation modelAllogeneic bone marrow transplantation modelAlloreactive donor T cellsGut-associated lymphoid tissueAdhesion moleculesMucosal addressin cell adhesion moleculeGVHD target organsMesenteric lymph nodesAlloreactive T cellsBone marrow transplantation modelMucosal lymphoid organsHigh endothelial venulesGVHD morbidityGVT activityIntestinal graftIntestinal GVHDLess graftLess GVHDHost diseaseLymph nodesDisease morbidityLymphoid organsLymphoid tissue