2025
Using TCR-CAR dual signaling for precise cancer targeting
Shahbazy M, Leo I, Faridi P, Caron E. Using TCR-CAR dual signaling for precise cancer targeting. Trends In Immunology 2025, 46: 435-437. PMID: 40368698, DOI: 10.1016/j.it.2025.04.007.Commentaries, Editorials and Letters
2024
Mechanism of Hyperactive PLCγ1 Signaling in T-Cell Leukemia/Lymphoma
Zeng L, Zhang X, Xiong Y, Hajicek N, Sondek J, Su X. Mechanism of Hyperactive PLCγ1 Signaling in T-Cell Leukemia/Lymphoma. Blood 2024, 144: 48-48. DOI: 10.1182/blood-2024-193065.Peer-Reviewed Original ResearchHDACi resistancePeripheral T-cell lymphomaCutaneous T-cell lymphomaAdult T-cell leukemia/lymphomaLiquid-liquid phase separationT-cell lymphomaT-cell leukemia/lymphomaT cell proliferationHistone deacetylasesTotal internal reflection fluorescenceT cellsTCR signalingDrug resistanceDysregulation of LLPSWild typeMolecular mechanismsAberrant protein aggregationInhibitor resistanceResistance to HDAC inhibitorsMemory T cell developmentT cell receptor signalingActivation of T cellsPromote T cell proliferationT-cell malignanciesBcl-2 expressionA non-catalytic role of IPMK is required for PLCγ1 activation in T cell receptor signaling by stabilizing the PLCγ1-Sam68 complex
Hong S, Kim K, Shim Y, Park J, Choi S, Min H, Lee S, Song J, Kang S, Jeong W, Seong R, Kim S. A non-catalytic role of IPMK is required for PLCγ1 activation in T cell receptor signaling by stabilizing the PLCγ1-Sam68 complex. Cell Communication And Signaling 2024, 22: 526. PMID: 39478550, PMCID: PMC11524019, DOI: 10.1186/s12964-024-01907-0.Peer-Reviewed Original ResearchConceptsInositol polyphosphate multikinaseT cell receptor signalingSrc family kinasesT cell receptorYeast two-hybrid screenFunctional protein-protein interactionsSrc-associated substrateTwo-hybrid screenNon-catalytic roleCD4+ T cellsProtein-protein interactionsPhosphatidylinositol 4,5-bisphosphateGrowth factor signalingC gamma 1Dominant-negative peptideNon-catalytic activitiesDownstream Signaling PathwaysQuantitative real-time PCRStimulation of T cell receptorSubstrate specificityPleiotropic enzymeProtein complexesFamily kinasesCo-ImmunoprecipitationT cells
2023
Machine learning-based cluster analysis of immune cell subtypes and breast cancer survival
Wang Z, Katsaros D, Wang J, Biglio N, Hernandez B, Fei P, Lu L, Risch H, Yu H. Machine learning-based cluster analysis of immune cell subtypes and breast cancer survival. Scientific Reports 2023, 13: 18962. PMID: 37923775, PMCID: PMC10624674, DOI: 10.1038/s41598-023-45932-4.Peer-Reviewed Original ResearchConceptsImmune cell clustersT cellsHost immunityImmune cellsUnsupervised hierarchical clusteringImmune responseCD8-positive T cellsMemory CD4 T cellsCox regression survival analysisRegulatory T cellsPositive T cellsCD4 T cellsDifferent immune cellsDistinct immune responsesBreast cancer survivalImmune cell subtypesMemory B cellsImmune cell typesRegression survival analysisCell clustersBreast cancer progressionT cell receptor signalingCytokine stormOverall survivalFavorable survivalEctocytosis renders T cell receptor signaling self-limiting at the immune synapse
Stinchcombe J, Asano Y, Kaufman C, Bohlig K, Peddie C, Collinson L, Nadler A, Griffiths G. Ectocytosis renders T cell receptor signaling self-limiting at the immune synapse. Science 2023, 380: 818-823. PMID: 37228189, PMCID: PMC7614748, DOI: 10.1126/science.abp8933.Peer-Reviewed Original ResearchConceptsCytotoxic T lymphocytesT cell receptorImmune synapseInduce negative membrane curvatureNegative membrane curvatureActivated T cell receptorT cell receptor signalingTarget cellsT cell receptor activationSelf-limitingOutward buddingProduction of diacylglycerolKill virus-infectedMembrane curvatureEctocytosisCancer cellsT lymphocytesDiacylglycerolEctosomesVirus infectionMembrane specializationsSynapseCellsEndocytosisKillingAdrenergic receptors regulate T cell differentiation in viral infection and cancer
Globig A, Zhao S, Roginsky J, Avina-Ochoa N, Heeg M, Chaudhary O, Hoffmann F, Chen D, O’Connor C, Emu B, Kaech S. Adrenergic receptors regulate T cell differentiation in viral infection and cancer. The Journal Of Immunology 2023, 210: 59.13-59.13. DOI: 10.4049/jimmunol.210.supp.59.13.Peer-Reviewed Original ResearchImmune checkpoint blockadeT cell differentiationChronic viral infectionsT cell functionalityT cellsViral infectionAdrenergic receptorsChronic antigen exposureLCMV clone 13Novel immune checkpointT cell proliferationMurine cancer modelsT cell receptor signalingCell differentiationAbstract CD8Terminal-CD8Exhausted CD8Checkpoint blockadeAntigen exposureImmune checkpointsNoradrenaline levelsCell receptor signalingTumor sizeCancer patientsNA receptors
2022
SILAC Phosphoproteomics Reveals Unique Signaling Circuits in CAR‑T Cells and the Inhibition of B Cell-Activating Phosphorylation in Target Cells
Griffith AA, Callahan KP, King NG, Xiao Q, Su X, Salomon AR. SILAC Phosphoproteomics Reveals Unique Signaling Circuits in CAR‑T Cells and the Inhibition of B Cell-Activating Phosphorylation in Target Cells. Journal Of Proteome Research 2022, 21: 395-409. PMID: 35014847, PMCID: PMC8830406, DOI: 10.1021/acs.jproteome.1c00735.Peer-Reviewed Original ResearchConceptsCD19 CAR T cellsChimeric antigen receptorRaji B cellsT cellsB cellsCAR T cell activityT cell activityB-cell malignanciesT cell receptor signalingCAR T cell signalingCell receptor signalingCD19-CARCell malignanciesT cell signalingCell activityReceptor signalingAntigen receptorLiquid chromatography-tandem mass spectrometryTarget cellsSignificant decreaseChromatography-tandem mass spectrometryTCR signalingReceptorsResponse of cellsCells
2019
An innate-like Vδ1+ γδ T cell compartment in the human breast is associated with remission in triple-negative breast cancer
Wu Y, Kyle-Cezar F, Woolf R, Naceur-Lombardelli C, Owen J, Biswas D, Lorenc A, Vantourout P, Gazinska P, Grigoriadis A, Tutt A, Hayday A. An innate-like Vδ1+ γδ T cell compartment in the human breast is associated with remission in triple-negative breast cancer. Science Translational Medicine 2019, 11 PMID: 31597756, PMCID: PMC6877350, DOI: 10.1126/scitranslmed.aax9364.Peer-Reviewed Original ResearchConceptsT cell compartmentT cell receptorTriple-negative breast cancerInnate-like responsesT cellsBreast cancerExpress T cell receptorsIFN-g productionProgression-free survivalHuman breastAntigen-specific responsesAssociated with remissionHuman breast tumorsT cell receptor signalingMaximal patient benefitProgression-FreeNKG2D receptorOverall survivalPeripheral bloodTissue-residentBreast tumorsIFN-gIL-17Paired tumorInflammatory pathology
2018
CD25-Dependent Feedback Control of the B-Cell Receptor and Its Oncogenic Mimics in B-Cell Malignancies
Lee J, Kume K, Chen Z, Xiao G, Cosgun K, Chan L, Chen C, Pillai R, Chan W, Forman S, Kwak L, Zammarchi F, Van Berkel P, Weinstock D, Melnick A, Ngo V, Geng H, Luger S, Litzow M, Belot A, Uzel G, McManus M, Paietta E, Meffre E, Muschen M. CD25-Dependent Feedback Control of the B-Cell Receptor and Its Oncogenic Mimics in B-Cell Malignancies. Blood 2018, 132: 776. DOI: 10.1182/blood-2018-99-117553.Peer-Reviewed Original ResearchB cell receptorReceptor chainsB-cell malignanciesNormal B cell developmentT cell receptor signalingB-cell leukemiaHomology-directed repairCell membrane translocationPoor clinical outcomeB cell developmentFeedback regulatorTransplant recipientsNegative feedback regulatorNegative feedback regulationCytoplasmic tailClinical outcomesGene expressionMolecule downstreamCytokine receptor chainsBCR signalingT cellsB cell selectionGenetic mouse modelsProliferation signalsAstra ZenecaPIP5 Kinases Regulate Membrane Phosphoinositide and Actin Composition for Targeted Granule Secretion by Cytotoxic Lymphocytes
Gawden-Bone C, Frazer G, Richard A, Y. C, Strege K, Griffiths G. PIP5 Kinases Regulate Membrane Phosphoinositide and Actin Composition for Targeted Granule Secretion by Cytotoxic Lymphocytes. Immunity 2018, 49: 427-437.e4. PMID: 30217409, PMCID: PMC6162341, DOI: 10.1016/j.immuni.2018.08.017.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCell DegranulationCell LineCell MembraneCytoplasmic GranulesCytotoxicity, ImmunologicImmunological SynapsesLymphocyte ActivationMiceMice, Inbred C57BLMice, TransgenicPhosphatidylinositolsPhosphotransferases (Alcohol Group Acceptor)Receptors, Antigen, T-CellSignal TransductionT-Lymphocytes, CytotoxicConceptsPlasma membraneGranule secretionSynapse formationT cell receptorArea of plasma membraneT cell receptor signalingImmune synapse formationActin depletionActin recruitmentPhosphoinositide compositionPIP5-kinaseCytotoxic T lymphocytesMembrane phosphoinositidesPI(4,5)P2Centrosome dockingActinTCR activationCell receptorsIncreased diacylglycerolPhosphoinositideSynapseDiacylglycerolForce localizationSecretionMembrane
2009
The Strength of T Cell Receptor Signal Controls the Polarization of Cytotoxic Machinery to the Immunological Synapse
Jenkins M, Tsun A, Stinchcombe J, Griffiths G. The Strength of T Cell Receptor Signal Controls the Polarization of Cytotoxic Machinery to the Immunological Synapse. Immunity 2009, 31: 621-631. PMID: 19833087, PMCID: PMC2791175, DOI: 10.1016/j.immuni.2009.08.024.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DegranulationCell PolarityCentrosomeCytoplasmic GranulesCytotoxicity, ImmunologicExtracellular Signal-Regulated MAP KinasesFemaleImmunological SynapsesMiceMice, Inbred C57BLMicroscopy, Electron, TransmissionOvalbuminPeptide FragmentsPhosphorylationReceptors, Antigen, T-CellSignal Transductionsrc-Family KinasesT-Lymphocytes, CytotoxicConceptsCytotoxic T lymphocytesCentral supramolecular activation complexT cell receptorT cell receptor signalingStrength of T cell receptor signalingImmunological synapseLytic granulesSupramolecular activation complexSecretion of lytic granulesLow-avidity interactionsGranule deliveryTarget cell deathCytotoxic machineryT lymphocytesGranule recruitmentGranule polarizationCentrosome polarizationReceptor signalingHigh-avidity interactionsPolar centrosomesCentrosomeCell deathIntracellular signalingSynapse
2002
Differential Requirement for LAT and SLP-76 in GPVI versus T Cell Receptor Signaling
Judd BA, Myung PS, Obergfell A, Myers EE, Cheng AM, Watson SP, Pear WS, Allman D, Shattil SJ, Koretzky GA. Differential Requirement for LAT and SLP-76 in GPVI versus T Cell Receptor Signaling. Journal Of Experimental Medicine 2002, 195: 705-717. PMID: 11901197, PMCID: PMC2193740, DOI: 10.1084/jem.20011583.Peer-Reviewed Original Research
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 RelationshipThymus GlandT-LymphocytesConceptsSLP-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
1995
CD4 and CD45 regulate qualitatively distinct patterns of calcium mobilization in individual CD4+ T cells
Leitenberg D, Constant S, Lu D, Smith B, Bottomly K. CD4 and CD45 regulate qualitatively distinct patterns of calcium mobilization in individual CD4+ T cells. European Journal Of Immunology 1995, 25: 2445-2451. PMID: 7589109, DOI: 10.1002/eji.1830250906.Peer-Reviewed Original ResearchConceptsIntracellular calcium concentrationCalcium mobilizationSustained increaseT cellsCell activationCalcium concentrationCross-linking CD4Antigen-presenting cellsIntracellular calcium mobilizationT cell interactionsT cell activationT cell receptor complexT cell receptor signalingDistinct patternsCell receptor signalingIndividual CD4Cell receptor complexCD4Extracellular calciumCD3Specific antigenCross-linking antibodiesCalcium spikesCalcium fluxReceptor signaling
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