2025
Transcription factor BACH2 shapes tissue-resident memory T cell programs to promote HIV-1 persistence
Wei Y, Katherine H, Wong M, Back H, Papasavvas E, Mounzer K, Aberra F, Morgenstern R, Tebas P, Konnikova L, Montaner L, Ho Y. Transcription factor BACH2 shapes tissue-resident memory T cell programs to promote HIV-1 persistence. Immunity 2025 DOI: 10.1016/j.immuni.2025.07.022.Peer-Reviewed Original ResearchCD8+ T cellsHIV-1 persistenceT cell receptorT cellsHIV-1Tissue residencyHIV-1-specific CD8+ T cellsLong-lived memoryEffector functionsTissue-resident memory T cellsHIV-1 immune evasionHIV-1-infected cellsHIV-1 DNAMemory T cellsHIV-1 RNAT cell programmingEffector memoryHIV- donorsCD4+Immune evasionMucosal immunityIn vitroSurface proteinsChromatin accessibilityTranscription factorsCo-expression network-based analysis of gene programs contributing to immune checkpoint inhibitor (ICI) resistance in renal cell carcinoma (RCC).
Malik R, Rout R, Kashima S, Saad E, Kane H, Shah V, Hugaboom M, Ye Z, Schindler N, Dighe A, Sun M, Lee G, Xu W, Signoretti S, McGregor B, McKay R, Atkins M, Van Allen E, Choueiri T, Braun D. Co-expression network-based analysis of gene programs contributing to immune checkpoint inhibitor (ICI) resistance in renal cell carcinoma (RCC). Journal Of Clinical Oncology 2025, 43: 4530-4530. DOI: 10.1200/jco.2025.43.16_suppl.4530.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsRenal cell carcinomaImmune cellsImmune infiltrationSignature scoreRCC tumor microenvironmentResistance to immune checkpoint inhibitorsAssociated with worse PFSICI-based therapyScRNA-seq dataGene programCD8+ TPhase II trialICI resistanceImmune-lowCheckpoint inhibitorsRibosomal proteinsCD4+II trialPrognostic roleRenal cell carcinoma tumor sampleRNA-seqCell carcinomaTumor microenvironmentScRNA-seqCas12a-knock-in mice for multiplexed genome editing, disease modelling and immune-cell engineering
Tang K, Zhou L, Tian X, Fang S, Vandenbulcke E, Du A, Shen J, Cao H, Zhou J, Chen K, Kim H, Luo Z, Xin S, Lin S, Park D, Yang L, Zhang Y, Suzuki K, Majety M, Ling X, Lam S, Chow R, Ren P, Tao B, Li K, Codina A, Dai X, Shang X, Bai S, Nottoli T, Levchenko A, Booth C, Liu C, Fan R, Dong M, Zhou X, Chen S. Cas12a-knock-in mice for multiplexed genome editing, disease modelling and immune-cell engineering. Nature Biomedical Engineering 2025, 1-19. PMID: 40114032, DOI: 10.1038/s41551-025-01371-2.Peer-Reviewed Original ResearchKnock-In MiceBone marrow-derived dendritic cellsCD8+ T cellsNon-viral delivery vehiclesAdeno-associated virusDisease modelsCD4+Dendritic cellsC57BL/6 backgroundT cellsConstitutive expressionB cellsLipid nanoparticlesEx vivoGenome editingMiceMultiplex genome engineeringROSA26 locusGene interaction networksMultiplex genome editingLiver tissueTargeted genome editingDiseaseDelivery vehiclesCRISPR RNAMachine learning-based spatial characterization of tumor-immune microenvironment in the EORTC 10994/BIG 1-00 early breast cancer trial
Zerdes I, Matikas A, Mezheyeuski A, Manikis G, Acs B, Johansson H, Boyaci C, Boman C, Poncet C, Ignatiadis M, Bai Y, Rimm D, Cameron D, Bonnefoi H, Bergh J, MacGrogan G, Foukakis T. Machine learning-based spatial characterization of tumor-immune microenvironment in the EORTC 10994/BIG 1-00 early breast cancer trial. Npj Breast Cancer 2025, 11: 23. PMID: 40055382, PMCID: PMC11889191, DOI: 10.1038/s41523-025-00730-1.Peer-Reviewed Original ResearchPathological complete responseAssociated with pathologic complete responseBreast cancerTriple-negativeCD8+ T cell expressionImmune infiltrate characterizationPretreatment tumor biopsiesTP53-mutated tumorsTumor immune microenvironmentTumor microenvironment componentsT cell expressionImmune cell subsetsTumors of patientsTumor-host interactionsBreast cancer trialsNeoadjuvant trialsComplete responseTN tumorsCD4+Tumor biopsiesCell subsetsPrognostic correlationPrognostic implicationsImmune infiltrationMultiplex immunofluorescenceLongitudinal CNS and systemic T-lymphocyte and monocyte activation before and after antiretroviral therapy beginning in primary HIV infection
Chan P, Li X, Li F, Emu B, Price R, Spudich S. Longitudinal CNS and systemic T-lymphocyte and monocyte activation before and after antiretroviral therapy beginning in primary HIV infection. Frontiers In Immunology 2025, 16: 1531828. PMID: 40070827, PMCID: PMC11893981, DOI: 10.3389/fimmu.2025.1531828.Peer-Reviewed Original ResearchConceptsCerebrospinal fluid HIV RNAPrimary HIV infectionT cell activationCD8+ T cell activationAntiretroviral therapyHIV RNACD4+HIV infectionCerebrospinal fluidT cellsMonocyte activationNeuronal injuryCD4+ T cell activationCD8<sup>+</sup> T cellsCD8+ T cellsFrequencies of activated CD4+ART-naive peopleChronic HIV infectionTrafficking of immune cellsAntiretroviral therapy initiationChemokine receptor expressionMultiparameter flow cytometryImmune cell activationSurface marker expressionCentral nervous systemAutogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial
Lopez J, Powles T, Braiteh F, Siu L, LoRusso P, Friedman C, Balmanoukian A, Gordon M, Yachnin J, Rottey S, Karydis I, Fisher G, Schmidt M, Schuler M, Sullivan R, Burris H, Galvao V, Henick B, Dirix L, Jaeger D, Ott P, Wong K, Jerusalem G, Schiza A, Fong L, Steeghs N, Leidner R, Rittmeyer A, Laurie S, Gort E, Aljumaily R, Melero I, Sabado R, Rhee I, Mancuso M, Muller L, Fine G, Yadav M, Kim L, Leveque V, Robert A, Darwish M, Qi T, Zhu J, Zhang J, Twomey P, Rao G, Low D, Petry C, Lo A, Schartner J, Delamarre L, Mellman I, Löwer M, Müller F, Derhovanessian E, Cortini A, Manning L, Maurus D, Brachtendorf S, Lörks V, Omokoko T, Godehardt E, Becker D, Hawner C, Wallrapp C, Albrecht C, Kröner C, Tadmor A, Diekmann J, Vormehr M, Jork A, Paruzynski A, Lang M, Blake J, Hennig O, Kuhn A, Sahin U, Türeci Ö, Camidge D. Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial. Nature Medicine 2025, 31: 152-164. PMID: 39762422, PMCID: PMC11750724, DOI: 10.1038/s41591-024-03334-7.Peer-Reviewed Original ResearchConceptsCD8+ T cellsAdvanced solid tumorsT cellsSolid tumorsCirculating CD8+ T cellsEfficacy of cancer immunotherapyTumor-infiltrating T cellsStimulate T cell responsesResponse to immunotherapyT cell responsesPreliminary antitumor activityPhase 1 studyPhase 1 trialDose escalationPretreated patientsCancer immunotherapyEvaluation of pharmacokineticsCD4+Tumor lesionsTreatment initiationTumor tissuesAtezolizumabClinical activityDisease characteristicsImmunotherapy
2024
Real-World Safety and Effectiveness of Dimethyl Fumarate in Patients with MS: Results from the ESTEEM Phase 4 and PROCLAIM Phase 3 Studies with a Focus on Older Patients
Mao-Draayer Y, Bar-Or A, Balashov K, Foley J, Smoot K, Longbrake E, Robertson D, Mendoza J, Lewin J, Everage N, Božin I, Lyons J, Mokliatchouk O, Bame E, Giuliani F. Real-World Safety and Effectiveness of Dimethyl Fumarate in Patients with MS: Results from the ESTEEM Phase 4 and PROCLAIM Phase 3 Studies with a Focus on Older Patients. Advances In Therapy 2024, 42: 395-412. PMID: 39570545, PMCID: PMC11782338, DOI: 10.1007/s12325-024-03047-w.Peer-Reviewed Original ResearchAbsolute lymphocyte countRelapsing-remitting MSEffect of dimethyl fumarateAnnualized relapse rateDisease-modifying therapiesAdverse eventsDimethyl fumarateCD8+ T cell compartmentMultiple sclerosisOlder patientsMedian absolute lymphocyte countOral disease-modifying therapyTreated with dimethyl fumarateSafety outcomesTreating relapsing MST cell compartmentPhase 3 studyResponse to disease-modifying therapiesIncidence of SAEsLymphocyte subset changesReal-world safetyTreatment discontinuationCD4+Immunophenotypic changesRelapse rate662 A phase1 study of autologous engineered CD4+ and CD8+ T cells, HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR; CD8α/β coreceptor and a FAS41BB switch receptor in patients with solid tumors
Mitchell S, Khan B, Payumo F, Gabriela Chiorean E, Gahvari Z, Randolph Hecht J, Hurwitz M, Leidner R, Lenz H, Pelster M, Schoenfeld A, Punekar S, Zhao D, Basu S, Nagorsen D. 662 A phase1 study of autologous engineered CD4+ and CD8+ T cells, HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR; CD8α/β coreceptor and a FAS41BB switch receptor in patients with solid tumors. 2024, a759-a759. DOI: 10.1136/jitc-2024-sitc2024.0662.Peer-Reviewed Original ResearchPhase I PIANO trial—PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes
Sundar R, Chia D, Zhao J, Lee A, Kim G, Tan H, Pang A, Shabbir A, Willaert W, Ma H, Huang K, Hagihara T, Tan A, Ong C, Wong J, Seo C, Walsh R, Chan G, Cheo S, Soh C, Callebout E, Geboes K, Ng M, Lum J, Leow W, Selvarajan S, Hoorens A, Ang W, Pang H, Tan P, Yong W, Chia C, Ceelen W, So J. Phase I PIANO trial—PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes. ESMO Open 2024, 9: 103681. PMID: 39288528, PMCID: PMC11421236, DOI: 10.1016/j.esmoop.2024.103681.Peer-Reviewed Original ResearchConceptsGastric cancer peritoneal metastasisPeritoneal cancer indexNivolumab combinationPeritoneal metastasisPeritoneal tumorsNaive CD8+ T cellsCD8+ central memoryEnhanced T cell infiltrationTreatment-related adverse eventsCD8+ T cellsGrade 4 vomitingRegression grade 1First-in-human trialImmune checkpoint inhibitionMemory CD4+T cell infiltrationImmunogenic cell deathSystemic immunotherapyCheckpoint inhibitionSystemic therapyCancer indexCD4+Intraperitoneal treatmentT cellsAdverse eventsTeplizumab induces persistent changes in the antigen‐specific repertoire in individuals at‐risk for type 1 diabetes
Lledó-Delgado A, Preston-Hurlburt P, Currie S, Clark P, Linsley P, Long S, Liu C, Koroleva G, Martins A, Tsang J, Herold K. Teplizumab induces persistent changes in the antigen‐specific repertoire in individuals at‐risk for type 1 diabetes. Journal Of Clinical Investigation 2024, 134: e177492. PMID: 39137044, PMCID: PMC11405034, DOI: 10.1172/jci177492.Peer-Reviewed Original ResearchCD8+ T cellsAutoreactive T cellsT cellsType 1 diabetesPeripheral blood CD8+ T cellsBlood CD8+ T cellsExpansion of autoreactive T cellsOperational toleranceExpression of CD127Progression of type 1 diabetesAnti-CD3 mAbAntigen-specific repertoireT cell receptorAt-risk patientsAnalysis of study participantsStudy participantsIL7R expressionTeplizumab groupCD8+Placebo groupCD4+Clinical respondersFree intervalTeplizumabReduced expression of genesNanoparticles loaded with IL-2 and TGF-β promote transplantation tolerance to alloantigen
Horwitz D, Wang J, Kim D, Kang C, Brion K, Bickerton S, La Cava A. Nanoparticles loaded with IL-2 and TGF-β promote transplantation tolerance to alloantigen. Frontiers In Immunology 2024, 15: 1429335. PMID: 39131162, PMCID: PMC11310063, DOI: 10.3389/fimmu.2024.1429335.Peer-Reviewed Original ResearchNP-treated miceT regulatory cellsMixed lymphocyte reactionDendritic cellsTolerogenic nanoparticlesAllogeneic cellsIL-2CD8+ T regulatory cellsGraft-versus-host diseaseAlloantigen-specific TregInhibition of mixed lymphocyte reactionTGF-bRecipient dendritic cellsGraft-versus-hostTolerogenic dendritic cellsResponse to alloantigensTolerance to alloantigensStrains of miceAlloantigen immunizationDecreased alloreactivityTolerogenic phenotypeCD4+Allogeneic splenocytesAllograft rejectionImmune suppressionAFNT-211: A phase 1 study of autologous CD4+ and CD8+ T cells engineered to express a high avidity HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR, a CD8α/β coreceptor, and a FAS41BB switch receptor in patients with advanced/metastatic solid tumors.
Mitchell S, Khan B, Payumo F, Chiorean E, Gahvari Z, Hecht J, Hurwitz M, Leidner R, Lenz H, Pelster M, Punekar S, Schoenfeld A, Zhao D, Vallaster M, Nagorsen D. AFNT-211: A phase 1 study of autologous CD4+ and CD8+ T cells engineered to express a high avidity HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR, a CD8α/β coreceptor, and a FAS41BB switch receptor in patients with advanced/metastatic solid tumors. Journal Of Clinical Oncology 2024, 42: tps8650-tps8650. DOI: 10.1200/jco.2024.42.16_suppl.tps8650.Peer-Reviewed Original ResearchOptimal biological doseCD8+ T cellsAutologous CD4+Advanced/metastatic solid tumorsT cellsSolid tumorsSwitch receptorsDose expansionDose escalationCD4+Transgenic TCRMechanism of actionDose-limiting toxicity observation periodRecommended phase 2 doseT cell cytotoxic activityIncreased T cell activationCD4+ T cellsHelper T cell responsesPreventing T cell exhaustionPost-treatment follow-up periodChimeric switch receptorsPhase 2 doseImmunosuppressive tumor microenvironmentT cell exhaustionDuration of responseReshaping immune cells and the antigen-specific repertoire by anti-CD3 mAb teplizumab in Type 1 diabetes
lledo delgado A, Preston-Hurlburt P, Currie S, Clark P, Herold K. Reshaping immune cells and the antigen-specific repertoire by anti-CD3 mAb teplizumab in Type 1 diabetes. The Journal Of Immunology 2024, 212: 0958_5059-0958_5059. DOI: 10.4049/jimmunol.212.supp.0958.5059.Peer-Reviewed Original ResearchCD8+ T cellsT cellsType 1 diabetesCD8+ T cell exhaustionAutoreactive CD8+ T cellsT cell exhaustionT cell changesCD8+ cellsProgression of type 1 diabetesAnti-CD3 mAbAntigen-specific repertoireAt-risk patientsCD8+CD4+Eomes expressionPeripheral bloodTeplizumabImmune cellsImmune regulationT1D diagnosisCD8Operational toleranceDelay progressionMonthsIndividuals at-risk
2004
618 Hpv16/18 E7-Pulsed Dendritic Cell Vaccination in Patients With Recurrent Cervical Cancer Refractory to Standard Salvage Therapy
Alessandro S, Stefania B, Juan R, Kay H, Pecorelli S. 618 Hpv16/18 E7-Pulsed Dendritic Cell Vaccination in Patients With Recurrent Cervical Cancer Refractory to Standard Salvage Therapy. International Journal Of Gynecological Cancer 2004, 14: 172. DOI: 10.1136/ijgc-00009577-200409001-00618.Peer-Reviewed Original ResearchDelayed-type hypersensitivityHuman papillomavirusDC vaccinesDendritic cellsE7 oncoproteinsCD8+ T cell infiltrationLow dose IL-2Standard salvage therapyDendritic cell vaccinesControl with surgeryT cell infiltrationFlu-like syndromeMature dendritic cellsMinor side effectsCervical cancer patientsTender indurationSalvage therapyImmunocompetent patientsDisseminated carcinomaRadiation therapyRecall antigensCD4+Clinical responseTherapeutic vaccinesE7 antigen
1998
Activated CD4+ and CD8+ cytotoxic cells are present in increased numbers in the intestinal mucosa from patients with active inflammatory bowel disease.
Müller S, Lory J, Corazza N, Griffiths G, Z'graggen K, Mazzucchelli L, Kappeler A, Mueller C. Activated CD4+ and CD8+ cytotoxic cells are present in increased numbers in the intestinal mucosa from patients with active inflammatory bowel disease. American Journal Of Pathology 1998, 152: 261-8. PMID: 9422543, PMCID: PMC1858122.Peer-Reviewed Original ResearchConceptsPerforin mRNA-expressing cellsInflammatory bowel diseaseMRNA-expressing cellsCytotoxic cellsGranzyme ACrohn's diseaseCD8+ T cellsCD8+ cytotoxic cellsBowel diseaseLamina propriaActive inflammatory bowel diseaseActivated cytotoxic cellsIntestinal mucosa of patientsActivated CD4+Cell-mediated cytotoxicityPathogenesis of inflammatory bowel diseaseMucosa of patientsIntestinal mucosaEpithelial cell layerSections of controlPerforin expressionCD4+Cells in situEpithelial compartmentT cells
1993
THE USE OF GRANZYME A AS A MARKER OF HEART TRANSPLANT REJECTION IN CYCLOSPORINE OR ANTI-CD4 MONOCLONAL ANTIBODY-TREATED RATS
CHEN R, IVENS K, ALPERT S, BILLINGHAM M, FATHMAN C, FLAVIN T, SHIZURU J, STARNES V, WEISSMAN I, GRIFFITHS G. THE USE OF GRANZYME A AS A MARKER OF HEART TRANSPLANT REJECTION IN CYCLOSPORINE OR ANTI-CD4 MONOCLONAL ANTIBODY-TREATED RATS. Transplantation 1993, 55: 146-153. PMID: 8420039, DOI: 10.1097/00007890-199301000-00027.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalBiomarkersCD4 AntigensCD4-CD8 RatioCyclosporineGraft RejectionGraft SurvivalGranzymesHeart TransplantationHistocompatibilityMaleRatsRats, Inbred ACIRats, Inbred LewSerine EndopeptidasesT-Lymphocytes, CytotoxicTransplantation, HomologousTransplantation, IsogeneicConceptsGranzyme A expressionA ExpressionGraft rejectionA+ cellsGranzyme AAnti-CD4 monoclonal antibodyCD8+ cytotoxic lymphocytesEvidence of graft rejectionAntibody-treated ratsIndefinite allograft survivalAnti-CD4 treatmentActivated CD4+Episodes of rejectionNatural killer cellsDonor-recipient combinationsMarker of graft rejectionMouse natural killer cellsIn situ hybridizationCardiac allograftsCD4/CD8 expressionAllograft survivalAnti-CD4Early time courseCD4+Autoimmune diabetes
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