2025
Mucosal unadjuvanted booster vaccines elicit local IgA responses by conversion of pre-existing immunity in mice
Kwon D, Mao T, Israelow B, Santos Guedes de Sá K, Dong H, Iwasaki A. Mucosal unadjuvanted booster vaccines elicit local IgA responses by conversion of pre-existing immunity in mice. Nature Immunology 2025, 26: 908-919. PMID: 40360777, DOI: 10.1038/s41590-025-02156-0.Peer-Reviewed Original ResearchMucosal immunityIgA responsesMemory CD4+ T cellsInduce robust mucosal immunitySARS-CoV-2 spike proteinCD4+ T cellsLocal protective immune responseRobust mucosal immunityRespiratory tractMRNA-LNP vaccinesIgA-secreting plasma cellsB cell recruitmentInduce mucosal immunityPre-existing immunityProtective immune responsesLower respiratory tractRecombinant SARS-CoV-2 spike proteinLocal IgA responseIntranasal boosterMucosal boostingIntranasal boostSpike proteinMRNA-LNPChemokines CXCL9T cellsPredicting adenine base editing efficiencies in different cellular contexts by deep learning
Kissling L, Mollaysa A, Janjuha S, Mathis N, Marquart K, Weber Y, Moon W, Lin P, Fan S, Muramatsu H, Vadovics M, Allam A, Pardi N, Tam Y, Krauthammer M, Schwank G. Predicting adenine base editing efficiencies in different cellular contexts by deep learning. Genome Biology 2025, 26: 115. PMID: 40340964, PMCID: PMC12060317, DOI: 10.1186/s13059-025-03586-7.Peer-Reviewed Original ResearchConceptsBase editing efficiencyEditing efficiencyCell linesPathogenic mutationsBase editingPrimary cells in vivoBase editing screensBase editing outcomesCells in vivoHEK293T cellsAdenine base editingIn vivo settingTarget lociT cellsLipid nanoparticlesCellular contextTarget sequenceMRNA deliveryBase pairsOn-target editingBystander effectEditing outcomesBase editorsIn vitro datasetsMurine liverMIF as an oncogenic driver of low‐heterogeneity melanomas
Tran T, Sánchez‐Zuno G, Kulkarni R, Kluger H, Bucala R. MIF as an oncogenic driver of low‐heterogeneity melanomas. Molecular Oncology 2025, 19: 1295-1298. PMID: 40131169, PMCID: PMC12077282, DOI: 10.1002/1878-0261.70031.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorImproving therapeutic outcomesMigration inhibitory factorPotential therapeutic utilityImmune landscapeMelanoma clonesImmune escapeT cellsImmunoregulatory cytokinesTumor heterogeneityTumor progressionOncogenic driversPathway inhibitorTherapeutic outcomesTumor evolutionInhibitory factorCell proliferationMelanomaTumorCellsAntagonistCytokinesDesign of sensitive monospecific and bispecific synthetic chimeric T cell receptors for cancer therapy
Simon S, Bugos G, Prins R, Rajan A, Palani A, Heyer K, Stevens A, Zeng L, Thompson K, Atilla P, Price J, Kluesner M, Jaeger-Ruckstuhl C, Shabaneh T, Olson J, Su X, Riddell S. Design of sensitive monospecific and bispecific synthetic chimeric T cell receptors for cancer therapy. Nature Cancer 2025, 1-19. PMID: 40097658, DOI: 10.1038/s43018-025-00927-0.Peer-Reviewed Original ResearchChimeric antigen receptorChimeric T cell receptorT cell receptorT cellsAdoptive transfer of T cells expressing chimeric antigen receptorsT cells expressing chimeric antigen receptorsChimeric antigen receptor T cellsBispecific CAR-T cellsPersistence of cancer cellsTCR-like signalsCAR-T cellsAntigen expression in vivoB-cell malignanciesMyeloma antigensExpression in vivoAdoptive transferEradicate tumorsAntigen sensitizationAntigen receptorFemale miceB cellsTumor heterogeneityPrevent relapseBispecific targetingImmune synapsesAberrant DNA methylation of genes regulating CD4+ T cell HIV‐1 reservoir in women with HIV
Xu K, Zhang X, Asam K, Quach B, Page G, Konkle‐Parker D, Martinez C, Lahiri C, Topper E, Cohen M, Kassaye S, DeHovitz J, Kuniholm M, Archin N, Valizadeh A, Tien P, Marconi V, Hancock D, Johnson E, Aouizerat B. Aberrant DNA methylation of genes regulating CD4+ T cell HIV‐1 reservoir in women with HIV. Clinical And Translational Medicine 2025, 15: e70267. PMID: 40070009, PMCID: PMC11896887, DOI: 10.1002/ctm2.70267.Peer-Reviewed Original ResearchConceptsCD4+ T cellsHIV-1 reservoirHIV-1 latencyT cellsHIV-1Aberrant DNA methylationMechanisms of HIV-1 latencyViral replicationVirally suppressed womenDNA methylationHIV-1 integration sitesHIV-1 replicationMolecular targetsDifferentially methylated CpG sitesImmune defenceDNA methylation sequencingHost epigenetic landscapeDNA methylation sitesHIV-1 DNA integrationDifferentially methylated sitesHost genome integrityInterferon signaling genesCure HIVHost-virus interactionsCD4A single-cell atlas of circulating immune cells over the first 2 months of age in extremely premature infants
Olaloye O, Gu W, Gehlhaar A, Sabuwala B, Eke C, Li Y, Kehoe T, Farmer R, Gabernet G, Lucas C, Tsang J, Lakhani S, Taylor S, Tseng G, Kleinstein S, Konnikova L. A single-cell atlas of circulating immune cells over the first 2 months of age in extremely premature infants. Science Translational Medicine 2025, 17: eadr0942. PMID: 40043141, DOI: 10.1126/scitranslmed.adr0942.Peer-Reviewed Original ResearchConceptsExtremely premature infantsFull-term infantsT cellsMonths of lifePremature infantsImmune cellsMemory CD4<sup>+</sup> T cellsCD4<sup>+</sup> T cellsMemory-like T cellsAnalysis of immune cellsNaive CD4<sup>+</sup>Peripheral T cell developmentWeeks of gestationCord blood samplesNatural killer cellsT helper 1B cell receptor sequencesT cell developmentCycling T cellsMonths of ageSingle-cell suspensionsAmount of bloodSusceptibility to infectionCD4<sup>+</sup>Killer cellsRNA cytidine acetyltransferase NAT10 maintains T cell pathogenicity in inflammatory bowel disease
Li H, Cai X, Xu C, Yang X, Song X, Kong Y, Yang M, Wu Q, Zheng S, Shao Y, Wang P, Zhou J, Li H. RNA cytidine acetyltransferase NAT10 maintains T cell pathogenicity in inflammatory bowel disease. Cell Discovery 2025, 11: 19. PMID: 40038243, PMCID: PMC11880361, DOI: 10.1038/s41421-025-00781-5.Peer-Reviewed Original ResearchAccelerated rate of apoptosisPost-transcriptional gene regulationBcl2-associated athanogene 3N-acetyltransferase 10Apoptosis-related genesUpregulation of apoptosis-related genesAcetyltransferase NAT10T cell developmentRate of apoptosisGene regulationApoptotic pathwayAc4C modificationN4-acetylcytidineCD4+ T cellsAcetylation modificationNAT10Inflammatory bowel diseaseMRNA stabilityNAT10 expressionDiminished stabilityT cellsN-acetyltransferaseRNAPathogensNaive CD4+ T cellsT cell exhaustion: early or late in tumour progression?
Galluzzi L. T cell exhaustion: early or late in tumour progression? Nature Reviews Immunology 2025, 1-2. PMID: 40038448, DOI: 10.1038/s41577-025-01158-1.Peer-Reviewed Original ResearchSensitive detection of synthetic response to cancer immunotherapy driven by gene paralog pairs
Dong C, Zhang F, He E, Ren P, Verma N, Zhu X, Feng D, Cai J, Zhao H, Chen S. Sensitive detection of synthetic response to cancer immunotherapy driven by gene paralog pairs. Patterns 2025, 6: 101184. DOI: 10.1016/j.patter.2025.101184.Peer-Reviewed Original ResearchParalogous gene pairsParalogous pairsChimeric antigen receptor T cellsResponse to cancer immunotherapyDouble knockoutCancer immunotherapy responseGene pairsCheckpoint blockadeGenome-wide screenImmunotherapy efficacyCancer immunotherapyEnhance immunotherapyImmunotherapy responseImmunotherapy effectT cellsImmunotherapyCancer treatmentIndividual genesCRISPR screensEnrichment analysisParalogsCancerTreatmentCombined targetFunctional significanceDEVELOPMENT OF EX VIVO PATIENT-DERIVED MODELS TO UNCOVER THE TUMOR-IMMUNE MICROENVIRONMENT IN RENAL CELL CARCINOMA
Kashima S, Gupta R, Moritz V, Sadak K, Walker J, Adeniran A, Humphrey P, Dinulescu D, Palmer D, Hammond S, Bosenberg M, Hurwitz M, Kenney P, Braun D. DEVELOPMENT OF EX VIVO PATIENT-DERIVED MODELS TO UNCOVER THE TUMOR-IMMUNE MICROENVIRONMENT IN RENAL CELL CARCINOMA. Urologic Oncology Seminars And Original Investigations 2025, 43: 22-23. DOI: 10.1016/j.urolonc.2024.12.057.Peer-Reviewed Original ResearchRCC tumor microenvironmentPatient-derived tumor modelsRenal cell carcinomaImmune checkpoint inhibitorsT cell functionTumor microenvironmentT cellsEnzyme-linked immunosorbent assayFlow cytometryTumor fragmentsTumor samplesCytokine productionImpact of immune checkpoint inhibitorsAnti-PD-1 monoclonal antibodyCD4+CD25+ regulatory T cellsResection of renal cell carcinomaSurgical resection of renal cell carcinomaCD8+ T cell populationsAnti-PD-1 antibodyMetastatic renal cell carcinomaCD20+ B cellsActivated CD8 T cellsEvaluate T cell activationT cell cytokine productionStudy of renal cell carcinomaComposition and function of AChR chimeric autoantibody receptor T cells for antigen-specific B cell depletion in myasthenia gravis
Oh S, Khani-Habibabadi F, O'Connor K, Payne A. Composition and function of AChR chimeric autoantibody receptor T cells for antigen-specific B cell depletion in myasthenia gravis. Science Advances 2025, 11: eadt0795. PMID: 40020066, PMCID: PMC11870065, DOI: 10.1126/sciadv.adt0795.Peer-Reviewed Original ResearchConceptsChimeric autoantibody receptorsMyasthenia gravisAnti-AChRChimeric autoantibody receptor T cellsSurface expressionSustained surface expressionTarget cell eliminationB-cell depletionT cell cytotoxicityB-cell outgrowthSevere muscle weaknessMouse xenograft modelSuppress immune functionCellular immunotherapyAChR-MGMg therapyT cellsB cellsXenograft modelMuscle weaknessImmune functionNeuromuscular transmissionCell eliminationCD28GravisNeoadjuvant cabozantinib for locally advanced nonmetastatic clear cell renal cell carcinoma: a phase 2 trial
Bilen M, Vo B, Liu Y, Greenwald R, Davarpanah A, McGuire D, Shiradkar R, Li L, Midya A, Nazha B, Brown J, Williams S, Session W, Russler G, Caulfield S, Joshi S, Narayan V, Filson C, Ogan K, Kucuk O, Carthon B, Del Balzo L, Cohen A, Boyanton A, Prokhnevska N, Cardenas M, Sobierajska E, Jansen C, Patil D, Nicaise E, Osunkoya A, Kissick H, Master V. Neoadjuvant cabozantinib for locally advanced nonmetastatic clear cell renal cell carcinoma: a phase 2 trial. Nature Cancer 2025, 6: 432-444. PMID: 40016487, DOI: 10.1038/s43018-025-00922-5.Peer-Reviewed Original ResearchConceptsNonmetastatic clear cell renal cell carcinomaRenal cell carcinomaClear cell renal cell carcinomaCell renal cell carcinomaCD8+ T cellsT cellsCell carcinomaAdverse eventsStem-like CD8+ T cellsMetastatic renal cell carcinomaPalmar-plantar erythrodysesthesia syndromeSingle-arm clinical trialOral multikinase inhibitorDisease-free survivalPhase 2 trialSecondary end pointsCabozantinib treatmentNeoadjuvant settingStable diseaseBiopsy-provenPartial responseSurgical resectionOverall survivalMultikinase inhibitorMyeloid populationsMigration arrest and transendothelial trafficking of human pathogenic-like Th17 cells are mediated by differentially positioned chemokines
Parween F, Singh S, Kathuria N, Zhang H, Ashida S, Otaizo-Carrasquero F, Shamsaddini A, Gardina P, Ganesan S, Kabat J, Lorenzi H, Riley D, Myers T, Pittaluga S, Bielekova B, Farber J. Migration arrest and transendothelial trafficking of human pathogenic-like Th17 cells are mediated by differentially positioned chemokines. Nature Communications 2025, 16: 1978. PMID: 40000641, PMCID: PMC11861662, DOI: 10.1038/s41467-025-57002-6.Peer-Reviewed Original ResearchConceptsEndothelial cellsTransendothelial migrationCCR2 ligandsFunction of CCR6Migration arrestChemokine receptor CCR6T cell receptor activationCerebrospinal fluid of patientsActivation-associated genesFluid of patientsActivated endothelial cellsEC surfaceTh17 signatureReceptor CCR6Th17 cellsT cellsChemokine receptorsCell extravasationInflammatory cytokinesReceptor activationCerebrospinal fluidCCR6ChemokinesMultiple sclerosisEnhanced expressionSingle cell analysis identifies distinct CD4 + T cells associated with the pathobiology of pediatric obesity related asthma
Thompson D, Wabara Y, Duran S, Reichenbach A, Chen L, Collado K, Yon C, Greally DMed J, Rastogi D. Single cell analysis identifies distinct CD4 + T cells associated with the pathobiology of pediatric obesity related asthma. Scientific Reports 2025, 15: 6844. PMID: 40000680, PMCID: PMC11861978, DOI: 10.1038/s41598-025-88423-4.Peer-Reviewed Original ResearchConceptsCD4+ T cellsT cell subtypesT cellsSteroid resistanceTh1 inflammationObese asthmaTh1 responseCentral memory T cellsObese asthma phenotypeEffector T cellsMemory T cellsObesity-related asthmaCD4+ T cell subtypesPediatric obesity-related asthmaT helper 1Healthy-weight controlsPulmonary function deficitsCD4Th1Asthma phenotypesGlucocorticoid receptorSingle-cell transcriptomicsFunctional deficitsInflammationSteroidsLongitudinal 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 systemHIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy
Jiang Q, Braun D, Clauser K, Ramesh V, Shirole N, Duke-Cohan J, Nabilsi N, Kramer N, Forman C, Lippincott I, Klaeger S, Phulphagar K, Chea V, Kim N, Vanasse A, Saad E, Parsons T, Carr-Reynolds M, Carulli I, Pinjusic K, Jiang Y, Li R, Syamala S, Rachimi S, Verzani E, Stevens J, Lane W, Camp S, Meli K, Pappalardi M, Herbert Z, Qiu X, Cejas P, Long H, Shukla S, Van Allen E, Choueiri T, Churchman L, Abelin J, Gurer C, MacBeath G, Childs R, Carr S, Keskin D, Wu C, Kaelin W. HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy. Cell 2025 PMID: 40023154, DOI: 10.1016/j.cell.2025.01.046.Peer-Reviewed Original ResearchClear cell renal cell carcinomaCancer immunotherapyAntigen-specific T cell responsesAllogeneic stem cell transplantationEndogenous retrovirusesClear cell renal cell carcinoma patientsLow mutational burdenCell renal cell carcinomaStem cell transplantationT cell responsesRenal cell carcinomaVHL tumor suppressor geneTumor suppressor geneHLA-bound peptidesEndogenous retrovirus expressionNon-ccRCCCell transplantationMutational burdenSpontaneous regressionCell carcinomaT cellsCase reportSuppressor geneHIF transcription factorsImmunotherapyPresence of tertiary lymphoid structures and exhausted tissue-resident T cells determines clinical response to PD-1 blockade in renal cell carcinoma.
Hugaboom M, Wirth L, Street K, Ruthen N, Jegede O, Schindler N, Shah V, Zaemes J, El Ahmar N, Matar S, Savla V, Choueiri T, Denize T, West D, McDermott D, Plimack E, Sosman J, Haas N, Stein M, Alter R, Bilen M, Hurwitz M, Hammers H, Signoretti S, Atkins M, Wu C, Braun D. Presence of tertiary lymphoid structures and exhausted tissue-resident T cells determines clinical response to PD-1 blockade in renal cell carcinoma. Cancer Discovery 2025, of1-of21. PMID: 39992403, DOI: 10.1158/2159-8290.cd-24-0991.Peer-Reviewed Original ResearchTertiary lymphoid structuresRenal cell carcinomaCD8+ T cellsAnti-PD1 monotherapyImmune checkpoint inhibitorsT cellsCell carcinomaLymphoid structuresClinical outcomesClinical response to PD-1 blockadeTreatment of advanced renal cell carcinomaResponse to PD-1 blockadePresence of tertiary lymphoid structuresAdvanced renal cell carcinomaTissue-resident T cellsPD-1 blockadePhase II clinical trialPD-1 pathwayCheckpoint inhibitorsICI resistancePD-1Responding patientsTumor microenvironmentTherapeutic responseTissue-residentPD-1H (VISTA) expression in cutaneous squamous cell carcinoma is correlated with T cell infiltration and activation
Kidacki M, Cho C, Lopez-Giraldez F, Huang B, He J, Gaule P, Chen L, Vesely M. PD-1H (VISTA) expression in cutaneous squamous cell carcinoma is correlated with T cell infiltration and activation. Journal Of Investigative Dermatology 2025 PMID: 39983979, DOI: 10.1016/j.jid.2025.01.030.Peer-Reviewed Original ResearchCutaneous squamous cell carcinomaPD-L1 expressionT cell infiltrationPD-L1Squamous cell carcinomaVISTA expressionPD-1HCell carcinomaT cellsBlockade of PD-1Proliferation marker Ki-67Multiplexed quantitative immunofluorescencePD-L1 coexpressionTreatment of cutaneous squamous cell carcinomaControl T cellsPreclinical cancer studiesMyeloid cell functionImmunosuppressive microenvironmentPD-1Receptor antagonismKi-67Individual tumorsGranzyme B.Clinical trialsCancer clinical trialsEnhanced paracrine action of FGF21 in stromal cells delays thymic aging
Youm Y, Gliniak C, Zhang Y, Dlugos T, Scherer P, Dixit V. Enhanced paracrine action of FGF21 in stromal cells delays thymic aging. Nature Aging 2025, 1-12. PMID: 39972172, DOI: 10.1038/s43587-025-00813-5.Peer-Reviewed Original ResearchThymic epithelial cellsThymic agingNaive CD8 T cellsCD8 T cellsAge-related thymic involutionT cell diversityThymic functionImmune dysfunctionThymic stromaT cellsThymic lymphopoiesisThymic involutionActions of FGF21Immune agingAged miceStromal cellsEpithelial cellsAged animalsCo-receptorHepatic overexpressionElevation of FGF21FGF21AgeCellsAdipocytesDendritic cell phagosomes recruit GRASP55 for export of antigen-loaded MHC molecules
Cebrian I, Dinamarca S, Rodríguez M, Priego E, Brouwers N, Barends M, Brunnberg J, Tampé R, Blanchard N, Sancho D, Malhotra V. Dendritic cell phagosomes recruit GRASP55 for export of antigen-loaded MHC molecules. Cell Reports 2025, 44: 115333. PMID: 39955774, PMCID: PMC11861518, DOI: 10.1016/j.celrep.2025.115333.Peer-Reviewed Original ResearchConceptsExogenous antigen presentationDendritic cellsAntigen presentationMHC moleculesBone marrow-derived dendritic cellsBone marrow-derived DCCD4<sup>+</sup> T cellsMHC-IActivated CD8<sup>+</sup>MHC class IIDendritic cell phagosomesMHC II moleculesCD8<sup>+</sup>Peptide-loaded MHC moleculesT cellsExogenous antigensMHC-IIClass IIAntigenEndocytic systemGRASP55Cell surfaceIntracellular transportPlasma membranePresentation
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