2023
Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation
Seike K, Kiledal A, Fujiwara H, Henig I, Burgos da Silva M, van den Brink M, Hein R, Hoostal M, Liu C, Oravecz-Wilson K, Lauder E, Li L, Sun Y, Schmidt T, Shah Y, Jenq R, Dick G, Reddy P. Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation. Immunity 2023, 56: 353-368.e6. PMID: 36736321, DOI: 10.1016/j.immuni.2023.01.007.Peer-Reviewed Original ResearchConceptsGraft-versus-host diseaseAmbient oxygen levelsGI graft-versus-host diseaseGut microbiome compositionMicrobiome-dependent mannerMicrobiome compositionMicrobial structureOxygen levelsIntestinal dysbiosisGraft-versus-host disease severityDysbiosisAllogeneic stem cell transplantationAnaerobic commensalsPathogenic T cellsStem cell transplantationIntestinal diseaseInflammatory bowel diseaseGastrointestinal (GI) diseasesCell transplantationIntestinal pathologyT cellsHostBowel diseaseHIF-1aIntestinal damage
2015
RIG-I-Induced Type I IFNs Promote Regeneration of the Intestinal Stem Cell Compartment during Acute Tissue Damage
Fischer J, Bscheider M, Eisenkolb G, Wintges A, Lindemans C, Heidegger S, Monette S, Calafiore M, Rodriguez K, Lieberman S, Liu C, Peschel C, Docampo M, Velardi E, Jenq R, Hanash A, Dudakov J, Haas T, van den Brink M, Poeck H. RIG-I-Induced Type I IFNs Promote Regeneration of the Intestinal Stem Cell Compartment during Acute Tissue Damage. Blood 2015, 126: 3072. DOI: 10.1182/blood.v126.23.3072.3072.Peer-Reviewed Original ResearchTotal body irradiationEpithelial regenerationAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationAcute intestinal injuryEpithelial cellsIntestinal barrier damageStem cell transplantationAcute tissue damageType I IFNsType I IFNActivation of RIGInnovative therapeutic strategiesIntestinal epithelial cellsRegenerative functionMechanism of actionHost diseaseIntestinal injuryBody irradiationBarrier damageCell transplantationDeficient miceViral challengePreclinical modelsWorse graft
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
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 approachesc‐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 targetAdoptively transferred TRAIL+ T cells suppress GVHD and augment antitumor activity
Ghosh A, Dogan Y, Moroz M, Holland A, Yim N, Rao U, Young L, Tannenbaum D, Masih D, Velardi E, Tsai J, Jenq R, Penack O, Hanash A, Smith O, Piersanti K, Lezcano C, Murphy G, Liu C, Palomba M, Sauer M, Sadelain M, Ponomarev V, van den Brink M. Adoptively transferred TRAIL+ T cells suppress GVHD and augment antitumor activity. Journal Of Clinical Investigation 2013, 123: 2654-2662. PMID: 23676461, PMCID: PMC3668849, DOI: 10.1172/jci66301.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntigen-Presenting CellsCell Line, TumorCytotoxicity, ImmunologicGraft RejectionGraft vs Host DiseaseHEK293 CellsHumansImmunotherapy, AdoptiveLeukemia, Lymphocytic, Chronic, B-CellMiceMice, Inbred BALB CMice, Inbred C57BLNeoplasm TransplantationT-LymphocytesTNF-Related Apoptosis-Inducing LigandConceptsGVT responseT cellsAllo-HSCTAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationCellular therapyAbsence of GVHDDR5-dependent mannerDonor T cellsAlloreactive T cellsStem cell transplantationChronic lymphocytic leukemia cellsPrecursor T cellsThird-party donorsLymphocytic leukemia cellsApoptosis-inducing ligandGVT activityHost diseaseCell transplantationCurative potentialTumor responseGVHDCertain malignanciesMouse modelHuman leukemia cell linesHost-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 disruptionRORγtPretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation
Hashimoto D, Chow A, Greter M, Saenger Y, Kwan W, Leboeuf M, Ginhoux F, Ochando J, Kunisaki Y, van Rooijen N, Liu C, Teshima T, Heeger P, Stanley E, Frenette P, Merad M. Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation. Journal Of Experimental Medicine 2011, 208: 1069-1082. PMID: 21536742, PMCID: PMC3092347, DOI: 10.1084/jem.20101709.Peer-Reviewed Original ResearchConceptsDonor allogeneic T cellsDonor T cell expansionAllogeneic hematopoietic cell transplantationAllogeneic T cellsHematopoietic cell transplantationAllo-HCTT cell expansionT cellsAcute GVHDCell transplantationHost macrophagesHost antigen-presenting cellsMacrophage poolPotential prophylactic therapyAlloreactive T cellsAntigen-presenting cellsAcute graftGVHD morbidityGVHD mortalityHost DCsHost diseaseProphylactic therapyRecipient miceGVHDRecipient macrophages
2010
Inhibition of Neovascularization to Simultaneously Ameliorate Graft-vs-Host Disease and Decrease Tumor Growth
Penack O, Henke E, Suh D, King C, Smith O, Na I, Holland A, Ghosh A, Lu S, Jenq R, Liu C, Murphy G, Lu T, May C, Scheinberg D, Gao D, Mittal V, Heller G, Benezra R, van den Brink M. Inhibition of Neovascularization to Simultaneously Ameliorate Graft-vs-Host Disease and Decrease Tumor Growth. Journal Of The National Cancer Institute 2010, 102: 894-908. PMID: 20463307, PMCID: PMC2886094, DOI: 10.1093/jnci/djq172.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAnimalsAntibodies, MonoclonalAntigens, CDBone Marrow TransplantationCadherinsFemaleFlow CytometryFluorescent Antibody TechniqueGraft vs Host DiseaseHematopoietic Stem Cell TransplantationMiceMice, Inbred C57BLNeoplasmsNeovascularization, PathologicTransplantation, HomologousConceptsTumor growthAllo-BMTHost diseaseAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationEndothelial cellsAllo-BMT recipientsGVHD target tissuesAllogeneic BM transplantationStem cell transplantationEndothelial progenitor cellsDecreases tumor growthInhibition of neovascularizationTumor-bearing miceTissue endothelial cellsAmeliorate graftDonor BMBM transplantationCell transplantationGVHDBone marrowTherapeutic targetingNeovascularizationOverall outcomeTumor vasculature
2007
288: A small molecular weight antagonist of CXCR3 reduces the severity of experimental idiopathic pneumonia syndrome and improves survival following allogeneic stem cell transplantation
Deurloo D, Chaudhary M, Olkiewicz K, Silva I, Choi S, Liu C, Collins T, Sullivan T, Cooke K. 288: A small molecular weight antagonist of CXCR3 reduces the severity of experimental idiopathic pneumonia syndrome and improves survival following allogeneic stem cell transplantation. Transplantation And Cellular Therapy 2007, 13: 105. DOI: 10.1016/j.bbmt.2006.12.293.Peer-Reviewed Original Research
2005
Absence of β7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine
Waldman E, Lu S, Hubbard V, Kochman A, Eng J, Terwey T, Muriglan S, Kim T, Heller G, Murphy G, Liu C, Alpdogan O, van den Brink M. Absence of β7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine. Blood 2005, 107: 1703-1711. PMID: 16291587, PMCID: PMC1895413, DOI: 10.1182/blood-2005-08-3445.Peer-Reviewed Original ResearchConceptsHematopoietic stem cell transplantationLess GVHD morbidityT cell infiltrationT cellsGVHD morbidityGVT activityHost diseaseDonor T-cell infiltrationDonor T cellsAlloreactive T cellsStem cell transplantationWild-type T cellsOverall significant decreaseIntestinal graftIntestinal GVHDLess graftBeta7 integrinCell transplantationCytokine productionAlpha4beta7 integrinIntact activationTumor experimentsMorbidityClinical potentialGraftCCR2 is required for CD8-induced graft-versus-host disease
Terwey T, Kim T, Kochman A, Hubbard V, Lu S, Zakrzewski J, Ramirez-Montagut T, Eng J, Muriglan S, Heller G, Murphy G, Liu C, Budak-Alpdogan T, Alpdogan O, van den Brink M. CCR2 is required for CD8-induced graft-versus-host disease. Blood 2005, 106: 3322-3330. PMID: 16037386, PMCID: PMC1895329, DOI: 10.1182/blood-2005-05-1860.Peer-Reviewed Original ResearchConceptsCC chemokine receptor 2Hematopoietic stem cell transplantationDevelopment of GVHDT cellsT cell migrationHost diseaseAllogeneic hematopoietic stem cell transplantationDonor-derived T cellsControl of CD8Donor-derived CD8GVHD target organsMurine bone marrow transplantation modelBone marrow transplantation modelStem cell transplantationChemokine receptor 2IFN-gamma productionWild-type CD8Alloreactive proliferationDonor CD8GVHD morbidityGVT activityTumor effectMajor complicationsCCR2 signalingCell transplantation
2004
Donor T-cell production of RANTES significantly contributes to the development of idiopathic pneumonia syndrome after allogeneic stem cell transplantation
Hildebrandt G, Olkiewicz K, Choi S, Corrion L, Clouthier S, Liu C, Serody J, Cooke K. Donor T-cell production of RANTES significantly contributes to the development of idiopathic pneumonia syndrome after allogeneic stem cell transplantation. Blood 2004, 105: 2249-2257. PMID: 15546955, DOI: 10.1182/blood-2004-08-3320.Peer-Reviewed Original ResearchConceptsIdiopathic pneumonia syndromeDevelopment of IPSAllogeneic stem cell transplantationDonor T cellsStem cell transplantationT cell responsesT cellsPneumonia syndromeAllo-SCTCell transplantationAlloreactive T cell responsesAllo-SCT recipientsInflammatory cell infiltrationT cell productionExpression of RANTESEnhanced mRNA expressionDonor leukocytesConditioning regimensLung injurySyngeneic controlsCell infiltrationChemokine ligandLeukocyte recruitmentRANTESTissue damageDonor T cell-derived TNF alpha regulates pulmonary chemokine expression and the development of idiopathic pneumonia syndrome after allogeneic stem cell transplantation
Hildebrandt G, Olkiewicz K, Corrion L, Chang Y, Liu C, Ferrara J, Cooke K. Donor T cell-derived TNF alpha regulates pulmonary chemokine expression and the development of idiopathic pneumonia syndrome after allogeneic stem cell transplantation. Transplantation And Cellular Therapy 2004, 10: 20. DOI: 10.1016/j.bbmt.2003.12.078.Peer-Reviewed Original Research
2003
108A role for the P75 but not the P55 TNFα receptor in the development of idiopathic pneumonia syndrome after allogeneic stem cell transplantation
Cooke K, Olkiewicz K, Erickson N, Hildebrandt G, Liu C, Ferrara J. 108A role for the P75 but not the P55 TNFα receptor in the development of idiopathic pneumonia syndrome after allogeneic stem cell transplantation. Transplantation And Cellular Therapy 2003, 9: 97. DOI: 10.1016/s1083-8791(03)80109-x.Peer-Reviewed Original Research