2021
Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells
Lucca LE, Axisa PP, Lu B, Harnett B, Jessel S, Zhang L, Raddassi K, Zhang L, Olino K, Clune J, Singer M, Kluger HM, Hafler DA. Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells. Journal Of Experimental Medicine 2021, 218: e20200921. PMID: 33651881, PMCID: PMC7933991, DOI: 10.1084/jem.20200921.Peer-Reviewed Original ResearchConceptsTumor-infiltrating T cellsT cellsUnique transcriptional patternsFeatures of exhaustionLongitudinal immune monitoringPeripheral immune environmentsT cell responsesT cell functionSingle-cell levelTranscriptional patternsTCR sharingTerminal exhaustionImmune environmentImmune monitoringCancer immunotherapyMetastatic melanomaEffector functionsCell responsesTumor tissueGene signatureTumorsCell functionImmunotherapyTCRαβBlood
2017
Co‐inhibitory blockade while preserving tolerance: checkpoint inhibitors for glioblastoma
Lucca LE, Hafler DA. Co‐inhibitory blockade while preserving tolerance: checkpoint inhibitors for glioblastoma. Immunological Reviews 2017, 276: 9-25. PMID: 28258696, PMCID: PMC5338636, DOI: 10.1111/imr.12529.Peer-Reviewed Original ResearchConceptsCheckpoint immunotherapyTumor rejectionCommon adult brain tumorsImmune-related side effectsCheckpoint receptor blockadeCo-inhibitory receptorsIntroduction of immunotherapyT cell exhaustionImmune regulatory pathwaysCo-inhibitory pathwaysAdult brain tumorsPrevention of autoimmunityCentral nervous systemAnti-tumor activityDifferent tumor typesCheckpoint inhibitorsReceptor blockadeAdvanced cancerTherapeutic successBrain tumorsSide effectsImmunotherapyNervous systemTherapeutic efficacyTumor types
2015
Prospects of immune checkpoint modulators in the treatment of glioblastoma
Preusser M, Lim M, Hafler DA, Reardon DA, Sampson JH. Prospects of immune checkpoint modulators in the treatment of glioblastoma. Nature Reviews Neurology 2015, 11: 504-514. PMID: 26260659, PMCID: PMC4782584, DOI: 10.1038/nrneurol.2015.139.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsClinical Trials as TopicGlioblastomaHumansImmunologic FactorsImmunotherapyConceptsImmune checkpoint inhibitorsCheckpoint inhibitorsGlioblastoma patientsMultiple immunosuppressive mechanismsMedian overall survivalImmune checkpoint modulatorsBlood-brain barrierTreatment of glioblastomaOverall survivalImmunosuppressive mechanismsAdvanced tumorsClinical benefitImmunotherapeutic agentsConventional therapyCheckpoint modulatorsLung cancerImmune systemPatientsCancerInhibitorsCurrent understandingImmunotherapyPrognosisLymphocytesTherapy
2010
FOXP3+ regulatory T cells in the human immune system
Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nature Reviews Immunology 2010, 10: 490-500. PMID: 20559327, DOI: 10.1038/nri2785.Peer-Reviewed Original ResearchConceptsForkhead box P3Human Treg cellsTreg cellsT cellsKey PointsRegulatory T (TReg) cellsTreg cell-based therapyAntitumour immune responseRegulatory T cellsExpression of CD45RAPromising therapeutic perspectiveHuman immune systemAutoimmune pathogenesisDominant toleranceBox P3HLA-DRCell-based therapiesAutoimmune diseasesImmune homeostasisImmune responseImmune diseasesSuppressive functionPotent mediatorCancer growthImmune systemTherapeutic perspectives
2008
Multiple Sclerosis and Regulatory T Cells
Costantino CM, Baecher-Allan C, Hafler DA. Multiple Sclerosis and Regulatory T Cells. Journal Of Clinical Immunology 2008, 28: 697-706. PMID: 18763026, PMCID: PMC2752287, DOI: 10.1007/s10875-008-9236-x.Peer-Reviewed Original ResearchConceptsRegulatory T cellsCentral nervous systemAutoreactive T cellsT cellsAntigen-specific Treg cellsAutoreactive effector T cellsAutoimmune tissue damageFrequency of TregsOrgan-specific autoimmunityEffector T cellsReactive T cellsBlood-brain barrierPathology of MSIntroductionMultiple sclerosisTreg cellsMS patientsPeripheral toleranceChronic inflammationMultiple sclerosisImmune disordersNew therapiesHealthy individualsNervous systemTissue damageDisease models
2002
Degeneracy, as opposed to specificity, in immunotherapy
Hafler DA. Degeneracy, as opposed to specificity, in immunotherapy. Journal Of Clinical Investigation 2002, 109: 581-584. PMID: 11877465, PMCID: PMC150898, DOI: 10.1172/jci15198.Peer-Reviewed Original Research
2000
Antigen-specific therapy for autoimmune disease
Harrison L, Hafler D. Antigen-specific therapy for autoimmune disease. Current Opinion In Immunology 2000, 12: 704-711. PMID: 11102776, DOI: 10.1016/s0952-7915(00)00166-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantigensAutoimmune DiseasesCytokinesHumansImmune ToleranceImmunotherapyMucous MembraneT-Lymphocytes
1996
Three‐year Open Protocol Continuation Study of Oral Tolerization with Myelin Antigens in Multiple Sclerosis and Design of a Phase III Pivotal Trial
HOHOL M, KHOURY S, COOK S, ORAV E, HAFLER D, WEINER H. Three‐year Open Protocol Continuation Study of Oral Tolerization with Myelin Antigens in Multiple Sclerosis and Design of a Phase III Pivotal Trial. Annals Of The New York Academy Of Sciences 1996, 778: 243-250. PMID: 8610977, DOI: 10.1111/j.1749-6632.1996.tb21132.x.Peer-Reviewed Original ResearchAntigen‐specific TGF‐β1 Secretion with Bovine Myelin Oral Tolerization in Multiple Sclerosis
FUKAURA H, KENT S, PIETRUSEWICZ M, KHOURY S, WEINER H, HAFLER D. Antigen‐specific TGF‐β1 Secretion with Bovine Myelin Oral Tolerization in Multiple Sclerosis. Annals Of The New York Academy Of Sciences 1996, 778: 251-257. PMID: 8610978, DOI: 10.1111/j.1749-6632.1996.tb21133.x.Peer-Reviewed Original ResearchConceptsRelapsing-remitting MS patientsHuman autoimmune diseasesOral tolerizationMultiple sclerosisAutoimmune diseasesT cell linesMS patientsCytokine secretionT cellsAutoreactive T-cell populationsAutoreactive T cellsT cell populationsT-cell fractionCNS white matterFed patientsIL-4Inflammatory responseΒ1 secretionIFN-gammaTolerizationWhite matterPatientsSclerosisBovine myelinSecretion
1995
Therapy for Multiple Sclerosis
Weiner H, Hohol M, Khoury S, Dawson D, Hafler D. Therapy for Multiple Sclerosis. Neurologic Clinics 1995, 13: 173-196. PMID: 7739502, DOI: 10.1016/s0733-8619(18)30066-5.Peer-Reviewed Original ResearchConceptsMultiple sclerosisCell-mediated autoimmune diseaseAccumulation of disabilityMultiple sclerosis patientsSymptomatic therapySclerosis patientsAutoimmune responseCentral nervous system myelinAutoimmune diseasesNonspecific modulationImmune systemSclerosisSystem myelinTherapyImmunotherapyPatientsDiseaseMyelinAntigen specific therapies for the treatment of autoimmune diseases.
Hafler DA, Weiner HL. Antigen specific therapies for the treatment of autoimmune diseases. 1995, 47: 59-77. PMID: 7785504, DOI: 10.1007/978-3-0348-7343-7_5.Peer-Reviewed Original Research
1993
The development of antigen specific therapies for autoimmune diseases; investigations in multiple sclerosis as a paradigm for rheumatoid arthritis.
Hafler DA, Zhang JW, LaSalle J, Donnelly C, Weiner HL, Wucherpfeffnig K. The development of antigen specific therapies for autoimmune diseases; investigations in multiple sclerosis as a paradigm for rheumatoid arthritis. Clinical And Experimental Rheumatology 1993, 11 Suppl 8: s39-40. PMID: 7686832.Peer-Reviewed Original Research
1992
T cell vaccination in multiple sclerosis: A preliminary report
Hafler D, Cohen I, Benjamin D, Weiner H. T cell vaccination in multiple sclerosis: A preliminary report. Clinical Immunology 1992, 62: 307-313. PMID: 1541056, DOI: 10.1016/0090-1229(92)90108-z.Peer-Reviewed Original ResearchMeSH KeywordsClone CellsHumansImmunotherapyLymphocyte ActivationMultiple SclerosisT-LymphocytesVaccinationConceptsT cell clonesMultiple sclerosisAutoimmune diseasesCell clonesAutologous T cell clonesAutoreactive T cell clonesAutologous mixed lymphocyte responseProgressive multiple sclerosisExperimental autoimmune diseasesT cell vaccinationFurther clinical trialsMixed lymphocyte responseUntoward side effectsCentral nervous systemPhase one trialsCell vaccinationMyelin autoantigensImmunologic effectsLymphocyte responsesClinical trialsImmunologic studiesAutoreactive clonesCerebrospinal fluidSide effectsNervous system
1991
Immunotherapy in autoimmune diseases
Miller A, Hafler D, Weiner H. Immunotherapy in autoimmune diseases. Current Opinion In Immunology 1991, 3: 936-940. PMID: 1793539, DOI: 10.1016/s0952-7915(05)80017-2.Peer-Reviewed Original ResearchConceptsAutoimmune diseasesImmunomodulatory therapeutic approachesHuman autoimmune diseasesMajor histocompatibility complex moleculesReceptor gene productsT cell recognitionHistocompatibility complex moleculesImmune interventionImmunological toleranceTherapeutic approachesAnimal modelsDiseaseImmunotherapyTrimolecular complexMolecular basisTolerance and suppressor mechanisms in experimental autoimmune encephalomyelitis: implications for immunotherapy of human autoimmune diseases
Miller A, Hafler D, Weiner H. Tolerance and suppressor mechanisms in experimental autoimmune encephalomyelitis: implications for immunotherapy of human autoimmune diseases. The FASEB Journal 1991, 5: 2560-2566. PMID: 1868980, DOI: 10.1096/fasebj.5.11.1868980.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisAutoimmune encephalomyelitisAutoimmune diseasesAnimal model experimental autoimmune encephalomyelitisModel experimental autoimmune encephalomyelitisHuman disease multiple sclerosisSpecific immune interventionAutoimmune T cellsHuman autoimmune diseasesNormal immune systemDisease multiple sclerosisMajor histocompatibility complexImmunospecific therapyTrimolecular complexImmune interventionSelective immunotherapyMultiple sclerosisT cellsImmune functionNonspecific modulationImmune systemAntigen recognitionHistocompatibility complexSuppressor mechanismDiseaseSuppression of experimental autoimmune encephalomyelitis by oral administration of myelin antigens: IV. Suppression of chronic relapsing disease in the lewis rat and strain 13 guinea pig
Brod S, al‐Sabbagh A, Sobel R, Hafler D, Weiner H. Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin antigens: IV. Suppression of chronic relapsing disease in the lewis rat and strain 13 guinea pig. Annals Of Neurology 1991, 29: 615-622. PMID: 1716432, DOI: 10.1002/ana.410290608.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisAutoimmune encephalomyelitisMyelin antigensGuinea pig myelinOral administrationCentral nervous systemLewis ratsMyelin basic proteinAntigen-specific peripheral immune toleranceGuinea pigsMonophasic experimental autoimmune encephalomyelitisDelayed-type hypersensitivity responseGuinea pig myelin basic proteinHuman demyelinating disordersOngoing immune responsePig myelin basic proteinComplete Freund's adjuvantPeripheral immune toleranceExacerbation of diseaseHuman autoimmune diseasesBasic proteinClinical relapseDemyelinating disorderOral toleranceCNS demyelination
1989
MS: a CNS and systematic autoimmune disease
Hafler D, Weiner H. MS: a CNS and systematic autoimmune disease. Trends In Immunology 1989, 10: 104-107. PMID: 2472810, DOI: 10.1016/0167-5699(89)90236-3.Peer-Reviewed Original ResearchConceptsPeripheral immune compartmentCentral nervous systemImmune compartmentMultiple sclerosisImmunoregulatory defectsMS patientsAutoimmune diseasesCNS inflammatory responsesTotal lymphoid irradiationProgressive multiple sclerosisT-cell abnormalitiesB cell hyperactivitySystemic lupus erythematosusT cell functionSystematic autoimmune diseaseActivated T cellsLymphoid irradiationDisease activityImmune abnormalitiesSystemic treatmentLupus erythematosusRheumatoid arthritisPeripheral bloodInflammatory diseasesInflammatory response
1988
Immunotherapy of multiple sclerosis
Weiner H, Hafler D. Immunotherapy of multiple sclerosis. Annals Of Neurology 1988, 23: 211-222. PMID: 3288084, DOI: 10.1002/ana.410230302.Peer-Reviewed Original ResearchConceptsMultiple sclerosisClinical trialsHelper/inducer cellsOnset of progressionMultiple sclerosis therapyNumber of relapsesPresent treatment modalitiesAntigen-specific cellsActivated T cellsImmune balanceImmunotherapeutic interventionsNonspecific immunosuppressionSclerosis therapyAcute attacksAutoimmune diseasesInducer cellsLymphocyte trafficTreatment modalitiesSuppressor influencesEarly treatmentT cellsEffective treatmentTherapeutic goalsImmunotherapyImmune system