2025
Why has immune “checkpoint” therapy failed in most clinical trials?
Yang X, Chen L. Why has immune “checkpoint” therapy failed in most clinical trials? Journal For ImmunoTherapy Of Cancer 2025, 13: e012457. PMID: 40866292, PMCID: PMC12410618, DOI: 10.1136/jitc-2025-012457.Peer-Reviewed Original ResearchConceptsTumor microenvironmentPD-1/PD-L1 pathwayTherapy-induced resistanceImmune evasion mechanismsAnti-PD therapyCheckpoint inhibitorsCancer immunotherapyTim-3Checkpoint targetsClinical benefitHematopoietic malignanciesSolid tumorsClinical developmentTherapeutic successAnti-PDClinical trialsEvasion mechanismsTumorCheckpointTIGITImmunotherapyMalignancyTherapyCancerMicroenvironment
2024
LAG-3, TIM-3, and TIGIT: Distinct functions in immune regulation
Joller N, Anderson A, Kuchroo V. LAG-3, TIM-3, and TIGIT: Distinct functions in immune regulation. Immunity 2024, 57: 206-222. PMID: 38354701, PMCID: PMC10919259, DOI: 10.1016/j.immuni.2024.01.010.Peer-Reviewed Original ResearchConceptsLAG-3Tim-3Immune cellsRestraining T-cell responsesImmune checkpoint receptorsT cell responsesRegulation of immune cellsImmune cell typesApplication of therapyPotential tissue toxicityCheckpoint receptorsTissue toxicityT cellsClinical developmentImmune regulationTIGITCell responsesReceptorsCell typesClinicCellsTherapy
2020
Differential expression of the T-cell inhibitor TIGIT in glioblastoma and MS
Lucca LE, Lerner BA, Park C, DeBartolo D, Harnett B, Kumar VP, Ponath G, Raddassi K, Huttner A, Hafler DA, Pitt D. Differential expression of the T-cell inhibitor TIGIT in glioblastoma and MS. Neurology Neuroimmunology & Neuroinflammation 2020, 7: e712. PMID: 32269065, PMCID: PMC7188477, DOI: 10.1212/nxi.0000000000000712.Peer-Reviewed Original ResearchConceptsTumor-infiltrating T cellsT cellsPD-1/PD-L1Anti-TIGIT therapyExpression of CD226Expression of TIGITPostmortem CNS tissueLymphocytes of patientsFresh surgical resectionsLigand CD155TIGIT expressionSurgical resectionPD-1PD-L1CNS diseaseHealthy controlsHealthy donorsLymphocytic expressionImmune responseCNS tissueMS lesionsTIGITImmune pathwaysPatientsGlioblastoma multiforme
2019
TIGIT signaling restores suppressor function of Th1 Tregs
Lucca LE, Axisa PP, Singer ER, Nolan NM, Dominguez-Villar M, Hafler DA. TIGIT signaling restores suppressor function of Th1 Tregs. JCI Insight 2019, 4: e124427. PMID: 30728325, PMCID: PMC6413794, DOI: 10.1172/jci.insight.124427.Peer-Reviewed Original ResearchIL-12Multiple sclerosisHuman autoimmune disordersT-bet expressionProinflammatory cytokine secretionProduction of IFNType 1 diabetesReduced suppressor activitySuppressor functionRepression of AktFOXO1 nuclear localizationTh1 programTIGIT pathwayCoinhibitory receptorsImmunomodulatory therapyTh17 responsesAutoimmune disordersAutoimmune diseasesSuppressor defectCytokine secretionTregsTIGITProtective effectFunctional inhibitionAkt pathwayIL-27 and TCR Stimulation Promote T Cell Expression of Multiple Inhibitory Receptors
DeLong JH, O'Hara Hall A, Rausch M, Moodley D, Perry J, Park J, Phan AT, Beiting DP, Kedl RM, Hill JA, Hunter CA. IL-27 and TCR Stimulation Promote T Cell Expression of Multiple Inhibitory Receptors. ImmunoHorizons 2019, 3: 13-25. PMID: 31356173, PMCID: PMC6994206, DOI: 10.4049/immunohorizons.1800083.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB7-H1 AntigenCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCostimulatory and Inhibitory T-Cell ReceptorsCTLA-4 AntigenFemaleInterleukinsLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLReceptors, Antigen, T-CellReceptors, ImmunologicSpleenToxoplasmaToxoplasmosisTranscriptomeTransfectionConceptsT cell expressionMultiple inhibitory receptorsIL-27Inhibitory receptorsPD-L1LAG-3Cell expressionCTLA-4Effector cell expressionTCR stimulationEffector T cellsIL-27 productionT cell activationTim-3Cell surface moleculesCell-extrinsic factorsT cellsIR expressionCell activationTIGITInfectionTCR signalsSurface moleculesSynergistic inductionVivo overexpression
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