2024
ARID1A suppresses R-loop-mediated STING-type I interferon pathway activation of anti-tumor immunity
Maxwell M, Hom-Tedla M, Yi J, Li S, Rivera S, Yu J, Burns M, McRae H, Stevenson B, Coakley K, Ho J, Gastelum K, Bell J, Jones A, Eskander R, Dykhuizen E, Shadel G, Kaech S, Hargreaves D. ARID1A suppresses R-loop-mediated STING-type I interferon pathway activation of anti-tumor immunity. Cell 2024, 187: 3390-3408.e19. PMID: 38754421, PMCID: PMC11193641, DOI: 10.1016/j.cell.2024.04.025.Peer-Reviewed Original ResearchImmune checkpoint blockadeAnti-tumor immunityIncreased CD8+ T cell infiltrationCD8+ T cell infiltrationT cell infiltrationType I IFN signalingGene expression signaturesICB treatmentCheckpoint blockadeIndependent of microsatellite instabilityARID1A mutationsCytolytic activityImmune phenotypeMurine modelCell infiltrationARID1A lossClinical trialsMutant cancersARID1AHuman cancersExpression signaturesGene upregulationMicrosatellite instabilityCancerInterferon
2023
Cytotoxic T lymphocytes require transcription for infiltration but not target cell lysis
Richard A, Y C, Marioni J, Griffiths G. Cytotoxic T lymphocytes require transcription for infiltration but not target cell lysis. EMBO Reports 2023, 24: e57653. PMID: 37860838, PMCID: PMC10626425, DOI: 10.15252/embr.202357653.Peer-Reviewed Original ResearchConceptsCytotoxic T lymphocytesT cell receptorT lymphocytesRelease of cytolytic granulesEffector cytotoxic T lymphocytesCytotoxic T lymphocyte functionCytotoxic protein expressionTarget cell lysisExpression of cytokines/chemokinesCytolytic activityActinomycin D treatmentCytolytic granulesTarget cellsCancer cellsTranscriptional blockadeProtein expressionInhibit transcriptionD treatmentInfiltrationTranscriptional requirementsCell lysisTranscriptomic changesCellsCytokines/chemokinesExpressionPrecision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells
Oh S, Mao X, Manfredo-Vieira S, Lee J, Patel D, Choi E, Alvarado A, Cottman-Thomas E, Maseda D, Tsao P, Ellebrecht C, Khella S, Richman D, O’Connor K, Herzberg U, Binder G, Milone M, Basu S, Payne A. Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells. Nature Biotechnology 2023, 41: 1229-1238. PMID: 36658341, PMCID: PMC10354218, DOI: 10.1038/s41587-022-01637-z.Peer-Reviewed Original ResearchConceptsMuscle‐specific tyrosine kinase myasthenia gravisReceptor T cellsB cellsT cellsMyasthenia gravisChimeric autoantibody receptor T cellsCD19 chimeric antigen receptor T cellsAutoantigen-specific B cellsChimeric antigen receptor T cellsAntigen receptor T cellsAnti-MuSK antibodiesB-cell depletionTotal IgG levelsClinical study designInvestigational new drug applicationChronic immunosuppressionIgG levelsMuscle weaknessAutoimmune diseasesCell depletionCurrent therapiesSimilar efficacyCytolytic activityMouse modelNew drug applications
2021
Epigenetic promoter alterations in GI tumour immune-editing and resistance to immune checkpoint inhibition
Sundar R, Huang K, Kumar V, Ramnarayanan K, Demircioglu D, Her Z, Ong X, Bin Adam Isa Z, Xing M, Tan A, Tai D, Choo S, Zhai W, Lim J, Thakur M, Molinero L, Cha E, Fasso M, Niger M, Pietrantonio F, Lee J, Jeyasekharan A, Qamra A, Patnala R, Fabritius A, De Simone M, Yeong J, Ng C, Rha S, Narita Y, Muro K, Guo Y, Skanderup A, So J, Yong W, Chen Q, Göke J, Tan P. Epigenetic promoter alterations in GI tumour immune-editing and resistance to immune checkpoint inhibition. Gut 2021, 71: 1277-1288. PMID: 34433583, PMCID: PMC9185816, DOI: 10.1136/gutjnl-2021-324420.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionImmune microenvironmentHuman immune systemCheckpoint inhibitionActive human immune systemGastric cancerHuman T-cell infiltrationT cell cytolytic activityResistance to immune checkpoint inhibitionImmune systemProgression-free survivalImmunotherapy-treated patientsT cell infiltrationTumor immune microenvironmentT cell proportionsImmune-editingImmunotherapy resistanceFunctional in vivo studiesTumor kineticsHumanised miceAlternative promoter useTumor microenvironmentTherapeutic responseCytolytic activityImmune depletion
2019
Loss of ARPC1B impairs cytotoxic T lymphocyte maintenance and cytolytic activity
Randzavola L, Strege K, Juzans M, Asano Y, Stinchcombe J, Gawden-Bone C, Seaman M, Kuijpers T, Griffiths G. Loss of ARPC1B impairs cytotoxic T lymphocyte maintenance and cytolytic activity. Journal Of Clinical Investigation 2019, 129: 5600-5614. PMID: 31710310, PMCID: PMC6877333, DOI: 10.1172/jci129388.Peer-Reviewed Original ResearchConceptsCD8 cytotoxic T lymphocytesLoss of CD8+ T cellsCD8+ T cell countsCD8+ T cellsViral infectionSymptoms of immune dysregulationT-cell countsRecurrent viral infectionsProlonged viral infectionCytotoxic T lymphocytesF-actinAdaptive immune responsesSecretion of lytic granulesActin-related protein 2/3Polarized secretion of lytic granulesT cell signalingTarget cell deathCTL cytotoxicityCTL activityF-actin networkCombined immunodeficiencyImmune dysregulationT cellsCytolytic activityT lymphocytesEpigenomic promoter alterations predict for benefit from immune checkpoint inhibition in metastatic gastric cancer
Sundar R, Huang K, Qamra A, Kim K, Kim S, Kang W, Tan A, Lee J, Tan P. Epigenomic promoter alterations predict for benefit from immune checkpoint inhibition in metastatic gastric cancer. Annals Of Oncology 2019, 30: 424-430. PMID: 30624548, PMCID: PMC6442650, DOI: 10.1093/annonc/mdy550.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionMetastatic gastric cancerT cell cytolytic activityResistance to immune checkpoint inhibitionCheckpoint inhibitionGastric cancerCytolytic activityImmune evasionMedian progression-free survivalPhase II clinical trial of patientsCancer treated with immunotherapyClinical trials of patientsMechanisms of immune evasionResponse rateTreated with pembrolizumabPhase II clinical trialProgression-free survivalFresh tumor biopsiesPost-treatment biopsiesCohort of patientsTrial of patientsEarly gastric cancerArchival tissue samplesClinical responseTumor biopsies
2017
The natural killer cell response to West Nile virus in young and old individuals with or without a prior history of infection
Yao Y, Strauss-Albee DM, Zhou JQ, Malawista A, Garcia MN, Murray KO, Blish CA, Montgomery RR. The natural killer cell response to West Nile virus in young and old individuals with or without a prior history of infection. PLOS ONE 2017, 12: e0172625. PMID: 28235099, PMCID: PMC5325267, DOI: 10.1371/journal.pone.0172625.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overAntigens, CDAsymptomatic DiseasesFemaleGene Expression RegulationHumansImmunity, InnateImmunophenotypingInterferon-gammaKiller Cells, NaturalLymphocyte ActivationLymphocyte CountMiddle AgedNatural Cytotoxicity Triggering Receptor 1Natural Cytotoxicity Triggering Receptor 2Natural Cytotoxicity Triggering Receptor 3NK Cell Lectin-Like Receptor Subfamily CNK Cell Lectin-Like Receptor Subfamily KPrimary Cell CultureSeverity of Illness IndexWest Nile FeverWest Nile virusConceptsNK cell subsetsNK cellsWest Nile virusWNV infectionCell subsetsCell responsesSpecific NK cell subsetsNatural killer cell responsesInnate NK cellsSevere neuroinvasive diseaseNK cell responsesNK cell receptorsNile virusHuman WNV infectionsImmune pathogenesisNK repertoirePolyfunctional responsesMore IFNSymptomatic infectionChemokine secretionAsymptomatic infectionNeuroinvasive diseasePrior historyCytolytic activityInfection
2013
Mg2+ Regulates Cytotoxic Functions of NK and CD8 T Cells in Chronic EBV Infection Through NKG2D
Chaigne-Delalande B, Li FY, O’Connor G, Lukacs MJ, Jiang P, Zheng L, Shatzer A, Biancalana M, Pittaluga S, Matthews HF, Jancel TJ, Bleesing JJ, Marsh RA, Kuijpers TW, Nichols KE, Lucas CL, Nagpal S, Mehmet H, Su HC, Cohen JI, Uzel G, Lenardo MJ. Mg2+ Regulates Cytotoxic Functions of NK and CD8 T Cells in Chronic EBV Infection Through NKG2D. Science 2013, 341: 186-191. PMID: 23846901, PMCID: PMC3894782, DOI: 10.1126/science.1240094.Peer-Reviewed Original ResearchConceptsEpstein-Barr virusNatural killerMagnesium transporter 1T cellsChronic EBV infectionCD8 T cellsIntracellular free magnesium concentrationEBV infectionCytolytic responsesCytotoxic functionReceptor NKG2DMagnesium supplementationBasal intracellularAntiviral immunityCytolytic activityFree magnesium concentrationNKG2DTransporter 1Genetic deficiencyDefective expressionCritical regulatorMagnesium concentrationKillerCellsIntracellular
2012
Phospholipid Scramblase 1 Mediates Type I Interferon-Induced Protection against Staphylococcal α-Toxin
Lizak M, Yarovinsky TO. Phospholipid Scramblase 1 Mediates Type I Interferon-Induced Protection against Staphylococcal α-Toxin. Cell Host & Microbe 2012, 11: 70-80. PMID: 22264514, PMCID: PMC3266557, DOI: 10.1016/j.chom.2011.12.004.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBacterial ToxinsBody TemperatureBody WeightCell LineCell SurvivalDisease Models, AnimalEpithelial CellsHemolysin ProteinsHumansInterferon-alphaLipoylationMiceMice, KnockoutPhospholipid Transfer ProteinsProtein Processing, Post-TranslationalStaphylococcal InfectionsStaphylococcus aureusSurvival AnalysisConceptsLung epithelial cellsI interferonΑ-toxinStaphylococcal α-toxinCytolytic activityPhospholipid scramblase 1Epithelial cellsInnate protective mechanismsCause of pneumoniaHuman lung epithelial cellsType I interferonAureus clinical isolatesPore-forming toxinsMajor virulence factorScramblase 1Intracellular ATP depletionPositive pathogen Staphylococcus aureusMice displayClinical isolatesAureus strainsProtective mechanismCellular depletionBacterial pore-forming toxinsVirulence factorsUnderlying mechanism
2010
Naturally Activated Vγ4 γδ T Cells Play a Protective Role in Tumor Immunity through Expression of Eomesodermin
He W, Hao J, Dong S, Gao Y, Tao J, Chi H, Flavell R, O’Brien R, Born WK, Craft J, Han J, Wang P, Zhao L, Wu J, Yin Z. Naturally Activated Vγ4 γδ T Cells Play a Protective Role in Tumor Immunity through Expression of Eomesodermin. The Journal Of Immunology 2010, 185: 126-133. PMID: 20525896, PMCID: PMC3813958, DOI: 10.4049/jimmunol.0903767.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCell Line, TumorCoculture TechniquesCytotoxicity, ImmunologicHyaluronan ReceptorsInterferon-gammaLymphocyte ActivationMelanoma, ExperimentalMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicPerforinReceptors, Antigen, T-Cell, gamma-deltaT-Box Domain ProteinsT-Lymphocyte SubsetsUp-RegulationConceptsGammadelta T cellsAntitumor immune responseT cellsImmune responseIFN-gammaTumor immunityProtective roleVγ4 γδ T cellsTumor immune surveillanceΓδ T cellsIFN-gamma secretionTumor immune therapyMore IFN-gammaGreater cytolytic activityExpression of EomesoderminAntitumor responseImmune therapyImmune surveillanceCytolytic activityEffector functionsPrincipal subsetsVgamma4Vgamma1Precise rolePerforin
2005
Induction of tumor NK-cell immunity by anti-CD69 antibody therapy
Esplugues E, Vega-Ramos J, Cartoixà D, Vazquez BN, Salaet I, Engel P, Lauzurica P. Induction of tumor NK-cell immunity by anti-CD69 antibody therapy. Blood 2005, 105: 4399-4406. PMID: 15692061, DOI: 10.1182/blood-2004-10-3854.Peer-Reviewed Original ResearchConceptsAntitumor responseNK cell cytolytic activityMonoclonal antibodiesCD69 monoclonal antibodiesNK cell immunityNK cytotoxic activityInterferon-gamma productionTGF-beta productionActivation marker CD69Production of cytokinesInnate immune systemReceptor-independent mannerNK cellsAntibody therapyLung metastasesCD69 expressionTherapeutic administrationCD69 mAbImmune responseCytolytic activityGamma productionImmune systemTumor growthTumor primingCD69
2002
A Non-class I MHC Intestinal Epithelial Surface Glycoprotein, gp180, Binds to CD8
Campbell N, Park M, Toy L, Yio X, Devine L, Kavathas P, Mayer L. A Non-class I MHC Intestinal Epithelial Surface Glycoprotein, gp180, Binds to CD8. Clinical Immunology 2002, 102: 267-274. PMID: 11890713, DOI: 10.1006/clim.2001.5170.Peer-Reviewed Original ResearchMeSH KeywordsAbsorptionAdaptor Proteins, Signal TransducingAnti-Bacterial AgentsAntibodies, MonoclonalBlotting, WesternCarcinoma, HepatocellularCarrier ProteinsCD40 AntigensCD8-Positive T-LymphocytesEnterocytesEnzyme-Linked Immunosorbent AssayEpitopesExtracellular Matrix ProteinsHumansImmediate-Early ProteinsLiver NeoplasmsMembrane GlycoproteinsPhosphorylationProteinsRecombinant Fusion ProteinsSequestosome-1 ProteinTransfectionTumor Cells, CulturedTunicamycinConceptsActivation of CD8T cellsIntestinal epithelial cellsCD8 moleculesEpithelial cellsMucosal immune responsesClass I MHCNormal intestinal epithelial cellsT cell activationMurine T cellsCD8 alphaImmune responseCytolytic activityI MHCCell activationMixed cell culture systemCD8Human CD8 alphaMonoclonal antibodiesCell culture systemActivationSurface glycoproteinTyrosine kinaseCellsGp180
2000
Direct Detection and Magnetic Isolation of Chlamydia trachomatis Major Outer Membrane Protein-Specific CD8+ CTLs with HLA Class I Tetramers
Kim S, Devine L, Angevine M, DeMars R, Kavathas P. Direct Detection and Magnetic Isolation of Chlamydia trachomatis Major Outer Membrane Protein-Specific CD8+ CTLs with HLA Class I Tetramers. The Journal Of Immunology 2000, 165: 7285-7292. PMID: 11120863, DOI: 10.4049/jimmunol.165.12.7285.Peer-Reviewed Original ResearchMeSH KeywordsBacterial Outer Membrane ProteinsCells, CulturedChlamydia trachomatisCytotoxicity Tests, ImmunologicEpitopes, T-LymphocyteFemaleHematopoietic Stem CellsHLA-A2 AntigenHLA-B AntigensHumansImmunomagnetic SeparationLymphocyte CountLymphogranuloma VenereumMalePorinsProtein BindingT-Lymphocytes, CytotoxicConceptsHLA class ITetramer-binding T cellsCTL responsesT cellsPeripheral bloodClass IPeptide-specific T cellsHLA-A2 tetramersPeptide-pulsed targetsGenital tract infectionElicit CTL responsesMajor Outer Membrane ProteinTetramer analysisTract infectionsPeptide stimulationImmunization trialsCytolytic activityChlamydia trachomatisUninfected individualsVivo inductionInfected individualsEpithelial cellsBloodBulk culturesStimulation
1992
A gamma delta+ T-cell leukemia bearing a novel t(8;14)(q24;q11) translocation demonstrates spontaneous in vitro natural killer-like activity.
Maziarz R, Arceci R, Bernstein S, Frazier L, Smith B, Kasai M, Tantravahi R, Strominger J. A gamma delta+ T-cell leukemia bearing a novel t(8;14)(q24;q11) translocation demonstrates spontaneous in vitro natural killer-like activity. Blood 1992, 79: 1523-31. PMID: 1532137, DOI: 10.1182/blood.v79.6.1523.bloodjournal7961523.Peer-Reviewed Original ResearchConceptsNatural killer-like activityT-cell leukemiaClinical conditionsNon-major histocompatibility complexPatient's clinical conditionGamma delta TCRTumor cell lysisFresh leukemic blastsDelta 1 gene segmentIntracellular calcium fluxGamma delta lineageT cell linesHuman T-cell leukemiaLeukemic blastsCytolytic activityDelta TCRLeukemia blastsC-myc proto-oncogene locusCalcium fluxCell surface analysisHistocompatibility complexDelta lineageLeukemiaLeukemia cellsProto-oncogene locusA γδ+ T-Cell Leukemia Bearing a Novel t(8;14)(q24;q11) Translocation Demonstrates Spontaneous In Vitro Natural Killer-Like Activity
Maziarz R, Arced R, Bernstein S, Frazier L, Smith B, Kasai M, Tantravahi R, Strominger J. A γδ+ T-Cell Leukemia Bearing a Novel t(8;14)(q24;q11) Translocation Demonstrates Spontaneous In Vitro Natural Killer-Like Activity. Blood 1992, 79: 1523-1531. DOI: 10.1182/blood.v79.6.1523.1523.Peer-Reviewed Original ResearchNatural killer-like activityT-cell leukemiaClinical conditionsNon-major histocompatibility complexPatient's clinical conditionGamma delta TCRTumor cell lysisFresh leukemic blastsDelta 1 gene segmentIntracellular calcium fluxGamma delta lineageT cell linesHuman T-cell leukemiaLeukemic blastsCytolytic activityDelta TCRLeukemia blastsC-myc proto-oncogene locusCalcium fluxCell surface analysisHistocompatibility complexDelta lineageLeukemiaLeukemia cellsProto-oncogene locus
1990
Natural killer lines and clones with apparent antigen specificity.
Suzuki N, Bianchi E, Bass H, Suzuki T, Bender J, Pardi R, Brenner C, Larrick J, Engleman E. Natural killer lines and clones with apparent antigen specificity. Journal Of Experimental Medicine 1990, 172: 457-462. PMID: 2142719, PMCID: PMC2188332, DOI: 10.1084/jem.172.2.457.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigen-Antibody ComplexAntigens, CDAntigens, DifferentiationAntigens, Differentiation, T-LymphocyteCD3 ComplexCell LineCells, CulturedClone CellsCytotoxicity, ImmunologicFlow CytometryHumansKiller Cells, NaturalMacromolecular SubstancesReceptors, Antigen, T-CellReceptors, FcReceptors, IgGConceptsLymphoblastoid cell linesAllogeneic lymphoblastoid cell linesTCR alpha/betaClass II MHC antigensIL-2-containing mediumPotent cytolytic activityNK cellsAllogeneic targetsCD3 lymphocytesMHC antigensCytolytic activityAntigen specificityTCR-beta transcriptsCD3Class ICD16CD3 epsilonSelective killingNorthern blot analysisBlot analysisCell linesK562 cellsK562 erythroleukemia cellsChain transcriptsMAbs
1989
Phenotypic and functional analysis of gamma delta T cell receptor-positive murine dendritic epidermal clones.
Havran W, Poenie M, Tigelaar R, Tsien R, Allison J. Phenotypic and functional analysis of gamma delta T cell receptor-positive murine dendritic epidermal clones. The Journal Of Immunology 1989, 142: 1422-8. PMID: 2783942, DOI: 10.4049/jimmunol.142.5.1422.Peer-Reviewed Original ResearchConceptsIL-2R expressionThy-1TCR complexSecretion of lymphokinesRelease of lymphokinesGamma delta TCRIntracellular free calciumEffect of antibodiesFunctional TCR complexDendritic cellsLy-6CPharmacologic agentsNormal miceT cellsCytolytic activityDelta TCRFree calciumGamma deltaAlpha betaDEC cellsCD3 complexEpidermal clonesProtein kinase CActivation signalsLymphokines
1988
Distinct molecular forms of human T cell receptor gamma/delta detected on viable T cells by a monoclonal antibody.
Borst J, van Dongen JJ, Bolhuis RL, Peters PJ, Hafler DA, de Vries E, van de Griend RJ. Distinct molecular forms of human T cell receptor gamma/delta detected on viable T cells by a monoclonal antibody. Journal Of Experimental Medicine 1988, 167: 1625-1644. PMID: 2966845, PMCID: PMC2188932, DOI: 10.1084/jem.167.5.1625.Peer-Reviewed Original ResearchConceptsTCR gamma/deltaT lymphocytesPeripheral bloodHuman TCR-gamma/deltaT cell receptor gamma/deltaGrowth factorGamma/deltaViable T cellsT cell clonesDistinct immune functionsTarget cell recognitionDifferent receptor typesHuman T lymphocytesCD8 antigenDelta antibodyIL-2Murine T lymphocytesT cellsCell surface iodinationCytolytic activityImmune functionReceptor typesLymphocytesTCR moleculesNormal individualsPhenotypic and functional characterization of human cytolytic T cells lacking expression of CD5.
Bierer BE, Nishimura Y, Burakoff SJ, Smith BR. Phenotypic and functional characterization of human cytolytic T cells lacking expression of CD5. Journal Of Clinical Investigation 1988, 81: 1390-1397. PMID: 2452832, PMCID: PMC442569, DOI: 10.1172/jci113468.Peer-Reviewed Original ResearchConceptsAnti-CD3 mAbNormal cytolytic activityCytolytic activityHuman cytolytic T cellsNormal individualsLymphocyte function-associated antigen-3Blood mononuclear cellsImmunofluorescence flow cytometryCytolytic T cellsExpression of CD5T lymphocyte clonesT cell activationSurface CD3Appropriate target cellsMononuclear cellsNormal CD5CD5 antigenT cellsIntracellular calciumLymphocyte clonesCD5Cell activationCell membrane glycoproteinAntigen 3Lymphoid phenotype
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