2024
Tertiary Lymphoid Structures and Immunotherapy: Challenges and Opportunities
Ruddle N. Tertiary Lymphoid Structures and Immunotherapy: Challenges and Opportunities. Methods In Molecular Biology 2024, 2864: 299-312. PMID: 39527229, DOI: 10.1007/978-1-0716-4184-2_16.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsImmune checkpoint inhibitorsTertiary lymphoid structuresSecondary lymphoid organsTA-TLSSusceptibility to immune-related adverse eventsAssociated with favorable clinical outcomesPositive response to immunotherapyResponse to immunotherapyFavorable clinical outcomesCellular compositionVascular growth factorsAccumulation of lymphoid cellsCheckpoint inhibitorsLymphoid neogenesisLymphoid structuresProcess of lymphoid neogenesisClinical outcomesAdenovirus vectorLymphoid cellsTumor-associatedAdverse eventsTumor environmentOrgan rejectionChronic inflammationMouse Models Enable the Functional Investigation of Tertiary Lymphoid Structures in Cancer
Jeevanandam A, Yin Z, Connolly K, Joshi N. Mouse Models Enable the Functional Investigation of Tertiary Lymphoid Structures in Cancer. Methods In Molecular Biology 2024, 2864: 57-76. PMID: 39527217, DOI: 10.1007/978-1-0716-4184-2_4.Peer-Reviewed Original ResearchConceptsTertiary lymphoid structuresTertiary lymphoid structure formationSecondary lymphoid organsLymphoid structuresMurine modelFeatures of tertiary lymphoid structuresFunction of tertiary lymphoid structuresMouse modelPersistent inflammatory stimulationAssociated with positive clinical outcomesTissue-specific regulatory mechanismsPositive clinical outcomesPrognostic significanceClinical outcomesGut environmentNonlymphoid tissuesLymphoid aggregatesLymphoid organsMouse lungCancer patientsGenetic sequencesInflammatory stimulationRegulatory mechanismsTherapeutic modulationClinical efforts
2023
Genetic Knockin Approaches to Reconstructing DLBCL-Subtypes from Human Germinal Center B-Cells
Khanduja D, Robinson M, Arce D, Klemm L, Leveille E, Kothari S, Caeser R, Hodson D, Müschen M. Genetic Knockin Approaches to Reconstructing DLBCL-Subtypes from Human Germinal Center B-Cells. Blood 2023, 142: 1627. DOI: 10.1182/blood-2023-190634.Peer-Reviewed Original ResearchSecondary lymphoid organsGerminal center B cellsMYD88 L265P mutationLymphoid organsLymph nodesB cellsL265P mutationHuman germinal center B cellsDLBCL subtypesNSG miceTonsillar germinal center B cellsLymphoma developmentPreclinical testingLymphoid tissue inducer cellsTransgenic expressionPoor clinical outcomeWild-type mutationsGenetic mouse modelsExon 5GC B cellsNBSGW miceClinical outcomesLTi cellsLymphoid folliclesInducer cellsT follicular helper cells in cancer, tertiary lymphoid structures, and beyond
Cui C, Craft J, Joshi N. T follicular helper cells in cancer, tertiary lymphoid structures, and beyond. Seminars In Immunology 2023, 69: 101797. PMID: 37343412, DOI: 10.1016/j.smim.2023.101797.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTumor-associated tertiary lymphoid structuresFollicular helper cellsCD8 T cellsTertiary lymphoid structuresSecondary lymphoid organsT cellsHelper cellsLymphoid structuresImmune cellsB cellsCD4 T follicular helper cellsT Follicular Helper CellsTumor-infiltrating immune cellsCurrent immunotherapy regimensCheckpoint blockade immunotherapyCD4 T cellsImmune cell componentsLimited response rateFunctional immune cellsNovel therapeutic targetPotential therapeutic benefitT cell-B cell interactionsBlockade immunotherapyImmunotherapy regimensLymphoid organs
2022
Dysregulated stem cell niches and altered lymphocyte recirculation cause B and T cell lymphopenia in WHIM syndrome
Zehentmeier S, Lim VY, Ma Y, Fossati J, Ito T, Jiang Y, Tumanov AV, Lee HJ, Dillinger L, Kim J, Csomos K, Walter JE, Choi J, Pereira JP. Dysregulated stem cell niches and altered lymphocyte recirculation cause B and T cell lymphopenia in WHIM syndrome. Science Immunology 2022, 7: eabo3170. PMID: 36149943, PMCID: PMC9614684, DOI: 10.1126/sciimmunol.abo3170.Peer-Reviewed Original ResearchConceptsSecondary lymphoid organsWHIM syndromeMesenchymal stem cellsInterleukin-7B lymphopeniaBone marrowBM mesenchymal stem cellsT cell numbersIL-7 productionT-cell lymphopeniaLymphotoxin beta receptorEarly progenitor stageLymphoid organsCell lymphopeniaMouse modelBeta receptorsB cellsB cell developmentLymphopeniaStromal cellsLeukocyte retentionSyndromeGOF mutationsLymphopoietic activityCritical pathways
2020
Basics of Inducible Lymphoid Organs
Ruddle NH. Basics of Inducible Lymphoid Organs. Current Topics In Microbiology And Immunology 2020, 426: 1-19. PMID: 32588229, DOI: 10.1007/82_2020_218.Peer-Reviewed Original ResearchConceptsTertiary lymphoid organsSecondary lymphoid organsLymphoid tissue organizerHigh endothelial venulesLymphoid organsDendritic cellsB cellsEctopic lymphoid organsFollicular dendritic cellsTertiary lymphoid structuresTertiary lymphoid tissueLymph nodesNK cellsChronic inflammationLTi cellsLymphoid structuresTolerance inductionInducer cellsLymphoid tissueEndothelial venulesAntigen presentationT cellsAccumulation of cellsStromal cellsAutoimmunity
2019
Cross-dressed dendritic cells sustain effector T cell responses in islet and kidney allografts
Hughes A, Zhao D, Dai H, Abou-Daya K, Tieu R, Rammal R, Williams A, Landsittel D, Shlomchik W, Morelli A, Oberbarnscheidt M, Lakkis F. Cross-dressed dendritic cells sustain effector T cell responses in islet and kidney allografts. Journal Of Clinical Investigation 2019, 130: 287-294. PMID: 31763998, PMCID: PMC6934226, DOI: 10.1172/jci125773.Peer-Reviewed Original ResearchConceptsHost DCT cell responsesDonor antigensT cellsMHC-peptide complexesActivation of host T cellsAlloantigens to T cellsEffector T cell responsesCD8+ T cellsDonor MHC moleculesHost T cellsDifferentiation to effectorKidney transplant modelSecondary lymphoid organsSelf-MHC moleculesAntigen presentation pathwayAcute rejectionAllograft rejectionDendritic cellsIndirect presentationTransplantation modelAntigen presentationLymphoid organsPresentation pathwayIntravital microscopySafety and pharmacodynamics of anti‐CD2 monoclonal antibody treatment in cynomolgus macaques – an experimental study
Berglund E, Alonso‐Guallart P, Danton M, Sellberg F, Binder C, Fröbom R, Berglund D, Llore N, Sakai H, Iuga A, Ekanayake‐Alper D, Reimann K, Sachs D, Sykes M, Griesemer A. Safety and pharmacodynamics of anti‐CD2 monoclonal antibody treatment in cynomolgus macaques – an experimental study. Transplant International 2019, 33: 98-107. PMID: 31523849, PMCID: PMC7017722, DOI: 10.1111/tri.13524.Peer-Reviewed Original ResearchConceptsAnti-CD2 treatmentT cellsStudy drug-related adverse eventsCynomolgus macaquesDrug-related adverse eventsEarly immune reconstitutionMemory T cellsLymph node examinationTreat transplant rejectionNaive T cellsMonoclonal antibody treatmentSecondary lymphoid organsMixed lymphocyte reactionAnti-CD2 monoclonal antibodiesImmune reconstitutionMLR inhibitionMemory subsetsNode examinationAntibody treatmentPeripheral bloodCD2 expressionLymphocyte reactionSafety profilePharmacodynamic profileTransplant rejectionAdaptive Immunity: Effector Functions, Regulation, and Vaccination
Kavathas P, Krause P, Ruddle N. Adaptive Immunity: Effector Functions, Regulation, and Vaccination. 2019, 75-95. DOI: 10.1007/978-3-030-25553-4_5.ChaptersAntigen-presenting cellsT cellsB cellsImmune responseInnate cellsEffector cellsInnate antigen-presenting cellsCD4 T helper cellsEffector T cellsB memory cellsT helper cellsSecondary lymphoid organsNaive T cellsBalanced immune responsePathogen-infected host cellsCD4 subsetCytokine milieuHelper cellsLymphoid organsEffector TPlasma cellsEffector functionsAdaptive immuneTypes of pathogensMacrophage responseOrganization and Cells of the Immune System
Kavathas P, Krause P, Ruddle N. Organization and Cells of the Immune System. 2019, 21-38. DOI: 10.1007/978-3-030-25553-4_2.ChaptersImmune cellsImmune systemLymphoid organsDifferent immune cell typesTertiary lymphoid organsInnate lymphoid cellsDifferent immune cellsSecondary lymphoid organsImmune cell typesLymphatic vesselsAdaptive immune systemHuman immune systemDendritic cellsBarrier immunityChronic inflammationUrinary tractSoluble mediatorsLymphoid cellsB cellsLymphoid systemMucosal surfacesChemokinesCytokinesOrgansCell typesMIF and MIF2 have distinct but synergistic roles in CIA pathogenesis
Doherty E, Tilstam P, Bucala R. MIF and MIF2 have distinct but synergistic roles in CIA pathogenesis. The Journal Of Immunology 2019, 202: 180.13-180.13. DOI: 10.4049/jimmunol.202.supp.180.13.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorRheumatoid arthritisT cellsCIA inductionCollagen-induced arthritis (CIA) mouse modelSevere erosive rheumatoid arthritisEffector memory T cellsCytokine macrophage migration inhibitory factorRelapsing autoimmune diseaseErosive rheumatoid arthritisProgressive joint destructionT cell infiltrationMemory T cellsAbstract Rheumatoid arthritisArthritis mouse modelSecondary lymphoid organsMigration inhibitory factorCIA pathogenesisHigh expression alleleJoint inflammationJoint destructionLymph nodesWT miceAutoimmune diseasesReceptor CD74T follicular helper cell heterogeneity: Time, space, and function
Song W, Craft J. T follicular helper cell heterogeneity: Time, space, and function. Immunological Reviews 2019, 288: 85-96. PMID: 30874350, PMCID: PMC6422039, DOI: 10.1111/imr.12740.Peer-Reviewed Original Research
2018
SHIP1 Inhibition As Novel Therapeutic Approach in Chronic Lymphocytic Leukemia
Ecker V, Braun M, Neumayer T, Muschen M, Ruland J, Buchner M. SHIP1 Inhibition As Novel Therapeutic Approach in Chronic Lymphocytic Leukemia. Blood 2018, 132: 894. DOI: 10.1182/blood-2018-99-117053.Peer-Reviewed Original ResearchChronic lymphocytic leukemiaMyeloid-derived suppressor cellsSecondary lymphoid organsImmune cell functionPeripheral bloodCLL cellsLymph nodesMalignant CLL cellsB cellsT cellsImmune responseLymphoid organsLymphocytic leukemiaSmall molecule inhibitorsSHIP1 inhibitionAge-matched healthy donorsAnti-tumor immune responsePharmacological inhibitionCell deathCLL peripheral bloodTreatment-related toxicityImmunoglobulin-producing plasma cellsRegulatory T cellsCell functionCLL cell deathGut pathobiont translocation induces lymphocyte migration to internal organs in autoimmunity
Fine R, Vieira S, Ruiz D, Kriegel M. Gut pathobiont translocation induces lymphocyte migration to internal organs in autoimmunity. The Journal Of Immunology 2018, 200: 102.16-102.16. DOI: 10.4049/jimmunol.200.supp.102.16.Peer-Reviewed Original ResearchC57BL/6 miceT cellsLymphocyte migrationInternal organsE. gallinarumProne C57BL/6 miceSystemic autoimmune diseaseSecondary lymphoid organsAutoimmune-prone (NZB/NZW) F1 miceGut homingGut pathobiontOral antibioticsSplenic CD4Autoantibody productionHost-microbiota interactionsAutoimmune diseasesSystemic autoimmunityLymphoid organsPeyer's patchesF1 miceMouse modelAutoimmunityPathobiontsMiceLymphocytes
2017
NIMG-36. DELINEATION OF IMMUNE RESPONSES AFTER IMMUNOTHERAPY IN GLIOBLASTOMA USING PET AND MRI
Soto H, Antonios J, Everson R, Moughon D, Wang A, Orpilla J, Radu C, Ellingson B, Lee J, Cloughesy T, Phelps M, Czernin J, Liau L, Prins R. NIMG-36. DELINEATION OF IMMUNE RESPONSES AFTER IMMUNOTHERAPY IN GLIOBLASTOMA USING PET AND MRI. Neuro-Oncology 2017, 19: vi149-vi150. PMCID: PMC5692246, DOI: 10.1093/neuonc/nox168.611.Peer-Reviewed Original ResearchPD-1Dendritic cellsMAb blockadeContrast enhancementHost anti-tumor immune responseTreated with dendritic cellsAnti-tumor immune responseInflammatory responseClinical management of patientsDendritic cell vaccinesTumor-infiltrating lymphocytesSyngeneic immunocompetent miceTreated with immunotherapyCo-registration of PETSecondary lymphoid organsContrast-enhanced MRIManagement of patientsProbe uptakePET probeImmune inflammatory responseNon-invasive modalityNon-invasive imaging techniqueImmunocompetent micePre-contrast T1Cell vaccineDetection of immune responses after immunotherapy in glioblastoma using PET and MRI
Antonios J, Soto H, Everson R, Moughon D, Wang A, Orpilla J, Radu C, Ellingson B, Lee J, Cloughesy T, Phelps M, Czernin J, Liau L, Prins R. Detection of immune responses after immunotherapy in glioblastoma using PET and MRI. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 10220-10225. PMID: 28874539, PMCID: PMC5617282, DOI: 10.1073/pnas.1706689114.Peer-Reviewed Original ResearchConceptsPD-1Dendritic cellsMAb blockadeTumor lysate-pulsed DC vaccineHost antitumor immune responseTreated with dendritic cellsImmune responseDetection of immune responsesClinical management of patientsPET probeAntitumor immune responseTumor-infiltrating lymphocytesSyngeneic immunocompetent miceContrast enhancementSecondary lymphoid organsContrast-enhanced MRIManagement of patientsProbe uptakeNoninvasive imaging techniquesImmune inflammatory responseDC vaccinesImmunocompetent miceIntracranial tumorsImaging techniquesMalignant gliomas
2016
High Endothelial Venules and Lymphatic Vessels in Tertiary Lymphoid Organs: Characteristics, Functions, and Regulation
Ruddle NH. High Endothelial Venules and Lymphatic Vessels in Tertiary Lymphoid Organs: Characteristics, Functions, and Regulation. Frontiers In Immunology 2016, 7: 491. PMID: 27881983, PMCID: PMC5101196, DOI: 10.3389/fimmu.2016.00491.Peer-Reviewed Original ResearchTertiary lymphoid organsHigh endothelial venulesSecondary lymphoid organsLymph nodesAntigen-presenting cellsLymphoid organsEndothelial venulesLymphatic vesselsStromal cellsCentral memory cellsPrimary lymphoid organsTransport antigensGraft rejectionEffector cellsChemokine expressionChronic inflammationPeyer's patchesAntigen presentationInflammatory signalsB cellsBone marrowImmune systemReticular cellsMicrobial infectionsCellular compositionBlocking MHC class II on human endothelium mitigates acute rejection
Abrahimi P, Qin L, Chang WG, Bothwell AL, Tellides G, Saltzman WM, Pober JS. Blocking MHC class II on human endothelium mitigates acute rejection. JCI Insight 2016, 1: e85293. PMID: 26900601, PMCID: PMC4756651, DOI: 10.1172/jci.insight.85293.Peer-Reviewed Original ResearchClass II MHC moleculesCytotoxic T lymphocytesII MHC moleculesClass I MHC moleculesMHC moleculesI MHC moleculesEndothelial cellsAcute rejectionT cellsEffector memory T cellsT cell-mediated destructionAcute allograft rejectionCell-mediated destructionGraft endothelial cellsMemory T cellsAlloreactive cytotoxic T lymphocytesExperimental rodent modelsMajor histocompatibility complex moleculesSecondary lymphoid organsMHC class IIClass I major histocompatibility complex moleculesAllogeneic human lymphocytesHistocompatibility complex moleculesPrevents CD4Artery graftTertiary Lymphoid Tissues
Ruddle N. Tertiary Lymphoid Tissues. 2016, 480-485. DOI: 10.1016/b978-0-12-374279-7.07012-0.Peer-Reviewed Original ResearchTertiary lymphoid organsTertiary lymphoid tissueSecondary lymphoid organsLymphoid organsLymphoid tissueConventional lymphoid organsChronic graft rejectionHigh endothelial venulesChronic microbial infectionsStromal cellular compositionAntigen primingNonlymphoid organsGraft rejectionDeterminant spreadingLymph nodesChronic inflammationEndothelial venulesClinical diseaseImmune responseInfectious organismsMicrobial infectionsCellular compositionLymphatic vesselsEctopic sitesAutoimmunity
2015
T Cell–Extrinsic CD18 Attenuates Antigen-Dependent CD4+ T Cell Activation In Vivo
Wu X, Lahiri A, Sarin R, Abraham C. T Cell–Extrinsic CD18 Attenuates Antigen-Dependent CD4+ T Cell Activation In Vivo. The Journal Of Immunology 2015, 194: 4122-4129. PMID: 25801431, PMCID: PMC4404034, DOI: 10.4049/jimmunol.1401328.Peer-Reviewed Original ResearchConceptsT cell activationCell proliferationAg-dependent T cell activationCell activationCell-extrinsic roleHematopoietic cellsEssential roleT cell proliferationCritical roleAdhesion moleculesΒ2 integrinsProliferationT cellsCellsActivationVivoActivation profilesAPCNaive T cellsSecondary lymphoid organsLeukocyte adhesion moleculesTraffickingRoleIntegrinsCD11b blockade
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