2024
Dominant negative variants in ITPR3 impair T cell Ca2+ dynamics causing combined immunodeficiency
Blanco E, Camps C, Bahal S, Kerai M, Ferla M, Rochussen A, Handel A, Golwala Z, Goncalves H, Kricke S, Klein F, Zhang F, Zinghirino F, Evans G, Keane T, Lizot S, Kusters M, Iro M, Patel S, Morris E, Burns S, Radcliffe R, Vasudevan P, Price A, Gillham O, Valdebenito G, Stewart G, Worth A, Adams S, Duchen M, André I, Adams D, Santili G, Gilmour K, Holländer G, Davies E, Taylor J, Griffiths G, Thrasher A, Dhalla F, Kreins A. Dominant negative variants in ITPR3 impair T cell Ca2+ dynamics causing combined immunodeficiency. Journal Of Experimental Medicine 2024, 222: e20220979. PMID: 39560673, PMCID: PMC11577440, DOI: 10.1084/jem.20220979.Peer-Reviewed Original ResearchConceptsStore-operated Ca2+ entryRelease of ER Ca2+Combined immunodeficiencyEndoplasmic reticulumDe novo missense variantDepletion of ER Ca2+ storesER Ca2+T cellsER Ca2+ storesDominant negative variantTriggers store-operated Ca2+ entryThymic T cell developmentInositol 1,4,5-trisphosphate receptorT cell developmentT-cell lymphopeniaT-cell immunodeficiencyCa2+ storesCa2+ entryCa2+ channelsMissense variantsT cell signalingPeripheral T cellsCa2+ homeostasisNegative variantsCa2+ dynamics
2023
First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors
Bendell J, LoRusso P, Overman M, Noonan A, Kim D, Strickler J, Kim S, Clarke S, George T, Grimison P, Barve M, Amin M, Desai J, Wise-Draper T, Eck S, Jiang Y, Khan A, Wu Y, Martin P, Cooper Z, Elgeioushi N, Mueller N, Kumar R, Patel S. First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors. Cancer Immunology, Immunotherapy 2023, 72: 2443-2458. PMID: 37016126, PMCID: PMC10264501, DOI: 10.1007/s00262-023-03430-6.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsPancreatic ductal adenocarcinomaColorectal cancerExpansion cohortHuman studiesResponse rateAnti-CD73 monoclonal antibodyProgression-free survival ratesTumor cellsMonoclonal antibodiesCommon being fatigueManageable safety profileObjective response rateAdvanced colorectal cancerAdvanced solid tumorsCell lung cancerPeripheral T cellsDate of registrationCD73 enzymatic activityAdverse eventsEscalation cohortsLocal immunosuppressionCD73 expressionSafety profileLung cancer
2020
IMMU-25. SEVERE AND MULTIFACETED SYSTEMIC IMMUNOSUPPRESSION CAUSED BY EXPERIMENTAL CANCERS OF THE CENTRAL NERVOUS SYSTEM REQUIRES RELEASE OF NON-STEROID SOLUBLE MEDIATORS
Ayasoufi K, Pfaller C, Evgin L, Khadka R, Tritz Z, Goddery E, Fain C, Yokanovich L, Himes B, Jin F, Zheng J, Schuelke M, Hansen M, Tung W, Parney I, Pease L, Vile R, Johnson A. IMMU-25. SEVERE AND MULTIFACETED SYSTEMIC IMMUNOSUPPRESSION CAUSED BY EXPERIMENTAL CANCERS OF THE CENTRAL NERVOUS SYSTEM REQUIRES RELEASE OF NON-STEROID SOLUBLE MEDIATORS. Neuro-Oncology 2020, 22: ii110-ii110. PMCID: PMC7650917, DOI: 10.1093/neuonc/noaa215.455.Peer-Reviewed Original ResearchT-cell countsCD4 T-cell countMHC class II expressionDiffuse intrinsic pontine gliomaClass II expressionThymic involutionT cellsCell countLow CD4 T-cell countsMHC class II expression levelPeripheral T-cell countsSignificant thymic involutionT cell sequestrationAcute neurological insultsCD4 T cellsHallmark featurePeripheral blood monocytesPeripheral T cellsNeurological disease modelsBlood-derived factorsIntrinsic pontine gliomaSystemic immunosuppressionGL261 gliomasBrain insultsCNS cancersChanges in Peripheral and Local Tumor Immunity after Neoadjuvant Chemotherapy Reshape Clinical Outcomes in Patients with Breast Cancer
Axelrod ML, Nixon MJ, Gonzalez-Ericsson PI, Bergman RE, Pilkinton MA, McDonnell WJ, Sanchez V, Opalenik SR, Loi S, Zhou J, Mackay S, Rexer BN, Abramson VG, Jansen VM, Mallal S, Donaldson J, Tolaney SM, Krop IE, Garrido-Castro AC, Marotti JD, Shee K, Miller TW, Sanders ME, Mayer IA, Salgado R, Balko JM. Changes in Peripheral and Local Tumor Immunity after Neoadjuvant Chemotherapy Reshape Clinical Outcomes in Patients with Breast Cancer. Clinical Cancer Research 2020, 26: 5668-5681. PMID: 32826327, PMCID: PMC7642197, DOI: 10.1158/1078-0432.ccr-19-3685.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAlbuminsAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenCD8-Positive T-LymphocytesFemaleGene Expression Regulation, NeoplasticHumansLymphocytes, Tumor-InfiltratingMiddle AgedNeoadjuvant TherapyNeoplasm ProteinsNeoplasm Recurrence, LocalPaclitaxelPrognosisProgrammed Cell Death 1 ReceptorProgression-Free SurvivalTreatment OutcomeTriple Negative Breast NeoplasmsTumor MicroenvironmentConceptsTriple-negative breast cancerTumor immune microenvironmentNeoadjuvant chemotherapyOverall survivalBreast cancerPeripheral bloodResidual diseaseMetastatic triple-negative breast cancerEffect of NACImproved long-term outcomesActive antitumor immunityLocal tumor immunityRole of chemotherapyT-cell signatureLong-term outcomesPeripheral T cellsMultiple immune-related genesImmune-related genesNab-paclitaxelImmunologic effectsMicrometastatic diseasePersistent diseaseAntitumor immunityTumor immunityClinical outcomesRandomized, phase II study of ficlatuzumab with or without cetuximab in patients with pan-refractory, recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).
Bauman J, Roe D, Saba N, Bauman J, Kaczmar J, Burtness B, Muzaffar J, Julian R, Wang S, Bearelly S, Baker A, Steuer C, Bhatia A, Giri A, Caulin C, Stabile L, Centuori S, Chung C. Randomized, phase II study of ficlatuzumab with or without cetuximab in patients with pan-refractory, recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Journal Of Clinical Oncology 2020, 38: tps6594-tps6594. DOI: 10.1200/jco.2020.38.15_suppl.tps6594.Peer-Reviewed Original ResearchProgression-free survivalOverall response rateM HNSCCPhase II trialHepatocyte growth factorII trialCetuximab resistanceMulticenter phase II trialRecurrent/metastatic headTotal peripheral T cellsRandomized phase II trialExpression of HGFPoor progression-free survivalNeck squamous cell carcinomaPeripheral immune profileKey secondary endpointPhase II studyKey eligibility criteriaSquamous cell carcinomaPeripheral T cellsPI3K/AktIgG1 monoclonal antibodyTwo-arm designECOG 0EGFR monotherapy
2018
Functional Alleles of Chicken BG Genes, Members of the Butyrophilin Gene Family, in Peripheral T Cells
Chen L, Fakiola M, Staines K, Butter C, Kaufman J. Functional Alleles of Chicken BG Genes, Members of the Butyrophilin Gene Family, in Peripheral T Cells. Frontiers In Immunology 2018, 9: 930. PMID: 29765375, PMCID: PMC5938342, DOI: 10.3389/fimmu.2018.00930.Peer-Reviewed Original ResearchConceptsCopy number variationsBG genesB12 haplotypeCytoplasmic tailFunctional allelesB2 haplotypeClosely-related genesUnequal crossing-overTruncated cytoplasmic tailPeripheral T cellsGene familyCoiled-coilAlternative splicingButyrophilin familyHeptad repeatNumber variationsCrossing-overHaplotypesPolar residuesGenesButyrophilinAllelesT cell ligandsCell typesT cells
2017
Oral treatment with foralumab, a fully human anti-CD3 monoclonal antibody, prevents skin xenograft rejection in humanized mice
Ogura M, Deng S, Preston-Hurlburt P, Ogura H, Shailubhai K, Kuhn C, Weiner HL, Herold KC. Oral treatment with foralumab, a fully human anti-CD3 monoclonal antibody, prevents skin xenograft rejection in humanized mice. Clinical Immunology 2017, 183: 240-246. PMID: 28739191, DOI: 10.1016/j.clim.2017.07.005.Peer-Reviewed Original ResearchConceptsSkin xenograft rejectionOral treatmentXenograft rejectionT cellsAnti-CD3 monoclonal antibodyConsecutive daily dosesPeripheral T cellsActivation of splenocytesHuman immune systemSplenic CD8Graft acceptanceWeekly dosingIL-10Serum levelsImmune therapySmall bowelHumanized miceDaily dosesImmune modulationMucosal barrierIntragastric doseOral administrationSkin graftsProliferative responseLymphoid cellsConcomitant Disruption of CD4 and CD8 Genes Facilitates the Development of Double Negative αβ TCR+ Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen
Chowdhary VR, Krogman A, Tilahun AY, Alexander MP, David CS, Rajagopalan G. Concomitant Disruption of CD4 and CD8 Genes Facilitates the Development of Double Negative αβ TCR+ Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen. The Journal Of Immunology 2017, 198: 4413-4424. PMID: 28468970, PMCID: PMC5471834, DOI: 10.4049/jimmunol.1601991.Peer-Reviewed Original ResearchConceptsDNT cellsDKO miceClass II moleculesΑβ TCRT cellsBacterial superantigensCD8 coreceptorIntact MHC class ILupus-like autoimmune diseaseEnterotoxin BHLA-DQ8 moleculesMHC class II moleculesAnti-nuclear AbsPeripheral T cellsDouble knockout miceMurine MHC class II moleculesMHC class IThymic positive selectionStaphylococcal enterotoxin BCD4/CD8 coreceptorsRegulatory cellsHLA-DR3Splenic CD3WT miceAutoimmune diseases
2015
Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis
Hwang SH, Jung SH, Lee S, Choi S, Yoo SA, Park JH, Hwang D, Shim SC, Sabbagh L, Kim KJ, Park SH, Cho CS, Kim BS, Leng L, Montgomery RR, Bucala R, Chung YJ, Kim WU. Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: e6535-e6543. PMID: 26554018, PMCID: PMC4664344, DOI: 10.1073/pnas.1514152112.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArthritis, ExperimentalArthritis, RheumatoidCalcium-Binding ProteinsCell MovementCells, CulturedChronic DiseaseExtracellular Signal-Regulated MAP KinasesGene DosageGene Expression ProfilingGenetic Predisposition to DiseaseHumansHypersensitivity, DelayedInflammationMiceMicrofilament ProteinsPhosphorylationReceptors, Antigen, T-CellT-LymphocytesConceptsT cell migrationRheumatoid arthritisT cellsImmune dysfunctionPathogenesis of RAPeripheral T cellsT cell activationT cell receptor activationProtein expression levelsLymph nodesChronic inflammationCytokine responsesInflamed synoviumAutoimmune diseasesLeukocyte-specific protein 1Primary T cellsRA susceptibilityReceptor activationDisease severityMigratory capacityLSP1 geneDiminished expressionTarget tissuesCell motilityProtein 1
2009
Development of a Reflex FISH Assay Panel for Lymphoid Neoplasms Resulted Negative by Cytogenetics and Current FISH Panel and Positive by Hematopathology.
Mitter N, Lanno S, Blackson J, Donskoy M, Ehrenpreis R. Development of a Reflex FISH Assay Panel for Lymphoid Neoplasms Resulted Negative by Cytogenetics and Current FISH Panel and Positive by Hematopathology. Blood 2009, 114: 4722. DOI: 10.1182/blood.v114.22.4722.4722.Peer-Reviewed Original ResearchFluorescence in situ hybridization panelAnaplastic large cell lymphomaFluorescence in situ hybridizationLarge cell lymphomaFISH panelLymphoid neoplasmsLoss of heterozygosityLocus-specific probesT cellsCell lymphomaKi-1+ anaplastic large cell lymphomaGene rearrangementsKi-1-positive anaplastic large cell lymphomaSubtype of non-Hodgkin lymphomaFluorescence in situ hybridization studiesNK/T-cell lymphomaT-cell disordersNon-Hodgkin's lymphomaT-cell lymphomaKi-1 antigenPeripheral T cellsProportion of patientsSpecific probesLow percentage of cellsRate of abnormalities
2008
The human T cell receptor Vβ repertoire of normal peripheral blood lymphocytes before and after mitogen stimulation
WONG F, HIBBERD M, WEN L, MILLWARD B, DEMAINF A. The human T cell receptor Vβ repertoire of normal peripheral blood lymphocytes before and after mitogen stimulation. Clinical & Experimental Immunology 2008, 92: 361-366. PMID: 8387412, PMCID: PMC1554814, DOI: 10.1111/j.1365-2249.1993.tb03405.x.Peer-Reviewed Original ResearchConceptsT cellsMitogen stimulationT cell antigen receptorPolymerase chain reactionT cell receptor Vβ repertoireFlow cytometryNormal peripheral blood lymphocytesMitogen-stimulated T cellsPeripheral blood lymphocytesTCR gene usagePeripheral T cellsT cell linesVβ repertoireUnstimulated T cellsBeta repertoireBlood lymphocytesHealthy individualsPCR methodBeta 6Cell antigen receptorGene usageAntigen receptorBeta 2Beta 5Chain reaction
2004
PLCβ Is Critical for T-Cell Chemotaxis In Vivo.
Bach T, Chen Q, Jordan M, Choi J, Wu D, Koretzky G, Zigmond S, Abrams C. PLCβ Is Critical for T-Cell Chemotaxis In Vivo. Blood 2004, 104: 2650. DOI: 10.1182/blood.v104.11.2650.2650.Peer-Reviewed Original ResearchT cell migrationT cellsChronic inflammationNeutrophil chemotaxisDense inflammatory infiltrateSecondary lymphoid organsWild-type T cellsType T cellsPeripheral T cellsWild-type miceMonths of ageWild-type lymphocytesT cell chemotaxisCytoplasmic calcium concentrationNull T cellsChemotactic responseKnockout T cellsInflammatory infiltrateRecipient miceLymphoid organsInflammatory responseSkin ulcersQuin-2 AMPlasma cellsT lymphocytes
2001
Differential Requirement for SLP-76 Domains in T Cell Development and Function
Myung P, Derimanov G, Jordan M, Punt J, Liu Q, Judd B, Meyers E, Sigmund C, Freedman B, Koretzky G. Differential Requirement for SLP-76 Domains in T Cell Development and Function. Immunity 2001, 15: 1011-1026. PMID: 11754821, DOI: 10.1016/s1074-7613(01)00253-9.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid MotifsAmino Acid SubstitutionAnimalsBinding SitesCalcium SignalingCarrier ProteinsCD3 ComplexCell DifferentiationClonal DeletionImmunophenotypingMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMutation, MissensePhosphoproteinsProtein Structure, TertiaryReceptors, Antigen, T-CellRecombinant Fusion ProteinsSequence DeletionSignal TransductionSpleensrc Homology DomainsStructure-Activity RelationshipT-LymphocytesThymus GlandConceptsSLP-76T cell developmentCell developmentDifferential requirementSLP-76 functionT cell receptor signalingCell receptor signalingAdaptor proteinMolecular mechanismsNull backgroundExamination of miceReceptor signalingCell functionPeripheral T cellsNew insightsTransgenic miceStructural requirementsSpecific domainsT cell functionT cellsCellsDomainMutantsThymocytesSignaling
1999
Mitotic recombination produces the majority of recessive fibroblast variants in heterozygous mice
Shao C, Deng L, Henegariu O, Liang L, Raikwar N, Sahota A, Stambrook P, Tischfield J. Mitotic recombination produces the majority of recessive fibroblast variants in heterozygous mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 9230-9235. PMID: 10430925, PMCID: PMC17762, DOI: 10.1073/pnas.96.16.9230.Peer-Reviewed Original ResearchMeSH KeywordsAdenine PhosphoribosyltransferaseAnimalsChromosome MappingCrosses, GeneticEar, ExternalExonsFemaleFibroblastsGenes, RecessiveGenetic VariationHeterozygoteHumansLoss of HeterozygosityMaleMiceMice, Inbred C3HMice, Inbred StrainsMice, Mutant StrainsMutagenesisPoint MutationRecombination, GeneticSkinT-LymphocytesConceptsMitotic recombinationPolymorphic molecular markersSomatic cell variantsProgeny of crossesFrequency of crossoversHigh spontaneous frequencyAPRT enzyme activitySomatic mutagenesisMap distanceCytological markersSelection mediumHuman peripheral T cellsMolecular markersChromosome 8Vivo lossCell coloniesAPRTEnzyme activityNormal fibroblastsRecombinationHeterozygous micePeripheral T cellsAdenine analogueHeterozygote miceVivo
1994
Analysis of the Peripheral T-Cell Receptor VP Repertoire in Newly Diagnosed Patients with Type I Diabetes
Wong S, Wen L, Hibberd M, Millward A, Demaine A. Analysis of the Peripheral T-Cell Receptor VP Repertoire in Newly Diagnosed Patients with Type I Diabetes. Autoimmunity 1994, 18: 77-83. PMID: 7999959, DOI: 10.3109/08916939409014682.Peer-Reviewed Original ResearchConceptsTCRBV gene usageGene usageSemi-quantitative polymerase chain reaction (PCR) techniqueType INormal healthy controlsBeta gene usagePeripheral T cellsT cell clonesPolymerase chain reaction techniqueClinical onsetHLA-DR3Chain reaction techniqueAutoimmune diseasesTCR repertoireHealthy controlsT cellsPatientsClinical diagnosisMarked activationSequential samplesSignificant differencesDiseaseDiagnosisDR4Cytometry
1986
Thy-1+ epidermal cells proliferate in response to concanavalin A and interleukin 2.
Nixon-Fulton J, Bergstresser P, Tigelaar R. Thy-1+ epidermal cells proliferate in response to concanavalin A and interleukin 2. The Journal Of Immunology 1986, 136: 2776-86. PMID: 2870120, DOI: 10.4049/jimmunol.136.8.2776.Peer-Reviewed Original ResearchConceptsPeripheral T cellsIL-2Langerhans cellsRat IL-2T cellsThy-1Con AAnti-T cell reagentsMature peripheral T cellsAKR/J miceComplement depletion studiesT-cell markersConcanavalin AFluorescence-activated cell sorterThy-1 antigenNK cellsMice 20Lyt-1Lyt-2J miceInterleukin-2Maximal responseMouse epidermal cellsAsialo GM1Day 5
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