2025
Molecular mechanisms of immune cell death in immunosenescence
Verduijn J, Coutant K, Fane M, Galluzzi L. Molecular mechanisms of immune cell death in immunosenescence. Cell Death & Differentiation 2025, 1-8. PMID: 40550879, DOI: 10.1038/s41418-025-01535-2.Peer-Reviewed Original ResearchActivation of regulated cell deathCell deathOrganismal agingImmune cell deathBone marrow defectImmune cell populationsImmune cell typesContext of immunosenescenceMolecular mechanismsNumerical alterationsThymic involutionMarrow defectCell typesImmune homeostasisImmune systemUnscheduled activitiesCell populationsImmunosenescenceFunctional degenerationMultiple compartmentsDeathPatterns of intra- and inter-tumor phenotypic heterogeneity in lethal prostate cancer
Roudier M, Gulati R, Sayar E, Patel R, Tratt M, Richards H, Cejas P, Gomez M, Qiu X, Xie Y, Hanratty B, Zaidi S, Zhao J, Adil M, Mittal C, Zhao Y, Dumpit R, Coleman I, Low J, Persse T, Galipeau P, Lee J, Tretiakova M, Chambers M, Vakar-Lopez F, True L, Perrone M, Lam H, Kollath L, Ding C, Harmon S, Cheng H, Yu E, Montgomery R, Hawley J, Lin D, Corey E, Schweizer M, Setty M, Ha G, Sawyers C, Morrissey C, Long H, Nelson P, Haffner M. Patterns of intra- and inter-tumor phenotypic heterogeneity in lethal prostate cancer. Journal Of Clinical Investigation 2025 PMID: 40493417, DOI: 10.1172/jci186599.Peer-Reviewed Original ResearchMetastatic prostate cancerLethal prostate cancerProstate cancerPhenotypic heterogeneityMetastatic prostate cancer patientsMolecularly heterogeneous diseaseTumor cell populationIntra-tumor heterogeneityCellular proliferation rateMetastatic sitesSingle-cell sequencing studiesMolecular subtypesClinical featuresTumor heterogeneityTumor phenotypeTumor samplesHeterogeneous diseaseClinical managementAnatomical sitesTherapeutic approachesSubtype heterogeneityPatientsTissue-basedCell populationsProliferation rateSingle-cell elderly blood–CSF atlas implicates peripherally influenced immune dysregulation in normal pressure hydrocephalus
Duy P, Kiziltug E, Greenberg A, Mehta N, Hao L, Fortes C, Mullany S, Fan B, Manichaikul A, Teich A, Chan D, Alper S, Hyman B, Arnold S, McKhann G, Frosch M, Kahle K. Single-cell elderly blood–CSF atlas implicates peripherally influenced immune dysregulation in normal pressure hydrocephalus. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2412159122. PMID: 40324076, PMCID: PMC12087963, DOI: 10.1073/pnas.2412159122.Peer-Reviewed Original ResearchConceptsIdiopathic normal pressure hydrocephalusNormal pressure hydrocephalusImmune dysregulationPeripheral bloodPressure hydrocephalusIdiopathic normal pressure hydrocephalus patientsProinflammatory alterationsVentricular CSFSingle-cell transcriptomicsINPH patientsCell populationsPatientsNeuroglial cellsCSFBloodHydrocephalusBaseline cognitive functionCognitive functionDysregulationMonocytesLung Marginal Zone-like B Cells: A Novel Pathogenic Immune Cell Population in Chronic Obstructive Pulmonary Disease
Zhao A, Rojas-Quintero J, Cong C, Zhang Y, Semenova A, Schiller H, San Jose Estepar R, Bhattacharya D, Sauler M, Polverino F. Lung Marginal Zone-like B Cells: A Novel Pathogenic Immune Cell Population in Chronic Obstructive Pulmonary Disease. American Journal Of Respiratory And Critical Care Medicine 2025, 211: a5246-a5246. DOI: 10.1164/ajrccm.2025.211.abstracts.a5246.Peer-Reviewed Original ResearchTargeting Polymeric Nanoparticles to Specific Cell Populations in the Liver
Harkins L, Vilarinho S, Saltzman W. Targeting Polymeric Nanoparticles to Specific Cell Populations in the Liver. Biochemistry 2025, 64: 1685-1697. PMID: 40127248, DOI: 10.1021/acs.biochem.4c00712.Peer-Reviewed Original ResearchConceptsLiver-resident macrophagesCell-specific targetingCell-specific deliveryAccumulation of nanoparticlesSpecific cell populationsDelivery of drugsConjugation of targeting ligandsTreatment of liver diseasesResident macrophagesKupffer cellsLiver diseaseNP administrationCell populationsConjugated nanoparticlesNP designDiseased liverSpecific deliveryCellular distributionTherapeutic carriersLiverSustained releaseNP characteristicsPolymer nanoparticlesCellsDeliveryNongenetic adaptation by collective migration
Vo L, Avgidis F, Mattingly H, Edmonds K, Burger I, Balasubramanian R, Shimizu T, Kazmierczak B, Emonet T. Nongenetic adaptation by collective migration. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2423774122. PMID: 39970001, PMCID: PMC11874451, DOI: 10.1073/pnas.2423774122.Peer-Reviewed Original ResearchConceptsGene regulationCollective migrationPhenotype distributionPhenotypic compositionStress response pathwaysSwimming phenotypeCell populationsBacterial populationsStress responseAbundance distributionMultidimensional phenotypesGenetic mutationsPhenotypeDiverse environmentsEnvironmental conditionsGenesMutationsSwimming behaviorChanging environmentDoubling timeMigrating populationCellsRegulationMigrationAdaptationSpatiotemporal dynamics of fetal liver hematopoietic niches
Peixoto M, Soares-da-Silva F, Bonnet V, Zhou Y, Ronteix G, Santos R, Mailhe M, Nogueira G, Feng X, Pereira J, Azzoni E, Anselmi G, de Bruijn M, Perkins A, Baroud C, Pinto-do-Ó P, Cumano A. Spatiotemporal dynamics of fetal liver hematopoietic niches. Journal Of Experimental Medicine 2025, 222: e20240592. PMID: 39775824, PMCID: PMC11706214, DOI: 10.1084/jem.20240592.Peer-Reviewed Original ResearchConceptsFetal liverSource of hematopoietic growth factorsStromal cellsNon-hematopoietic stromal cellsHematopoietic growth factorsCytokine production patternsStromal cell populationsNeighboring stromal cellsEmbryonic hematopoietic cellsFetal hematopoiesisComplex cellular interactionsHematopoietic progenitorsHematopoietic cellsGrowth factorCell populationsFL developmentCellular interactionsCellsDevelopmental changesSignaling networks
2024
Biodistribution of Polymeric Nanoparticles following in utero Delivery to a Nonhuman Primate
Eaton D, Lynn A, Surprenant J, Deschenes E, Guerra M, Rivero R, Yung N, O'Connor M, Glazer P, Bahtiyar M, Saltzman W, Stitelman D. Biodistribution of Polymeric Nanoparticles following in utero Delivery to a Nonhuman Primate. Biomedicine Hub 2024, 10: 543138. PMID: 39845408, PMCID: PMC11753793, DOI: 10.1159/000543138.Peer-Reviewed Original ResearchMonogenic diseasesNon-human primatesBiodistribution of polymeric nanoparticlesPreclinical mouse modelsStem cell populationFetal liverFetal malesSystemic deliveryFetal bonesAccumulation of NPIn-uteroMid-gestationNP accumulationBiodistribution studiesPolymeric NPsTherapeutic accessCell populationsMaternal tissuesZone of proliferationPolymeric nanoparticlesDiseaseBirthMiceDeliveryBiodistributionGold-siRNA supraclusters enhance the anti-tumor immune response of stereotactic ablative radiotherapy at primary and metastatic tumors
Jiang Y, Cao H, Deng H, Guan L, Langthasa J, Colburg D, Melemenidis S, Cotton R, Aleman J, Wang X, Graves E, Kalbasi A, Pu K, Rao J, Le Q. Gold-siRNA supraclusters enhance the anti-tumor immune response of stereotactic ablative radiotherapy at primary and metastatic tumors. Nature Biotechnology 2024, 1-14. PMID: 39448881, PMCID: PMC12018592, DOI: 10.1038/s41587-024-02448-0.Peer-Reviewed Original ResearchStereotactic ablative radiotherapyAnti-tumor immune responseSmall interfering RNAAblative radiotherapyMetastatic tumorsEffect of stereotactic ablative radiotherapyModel of head and neck cancerHead and neck cancerImmunosuppressive cell populationsPD-1 inhibitorsSmall interfering RNA complexesPD-1Primary tumorImmunotherapeutic effectsNeck cancerGranzyme BGal-1Mouse modelPassive deliveryTumorReduced toxicityCell populationsRadiotherapyRadiosensitivityRenal filtration thresholdParameter optimization for stable clustering using FlowSOM: a case study from CyTOF
Tao W, Sinha A, Raddassi K, Pandit A. Parameter optimization for stable clustering using FlowSOM: a case study from CyTOF. Frontiers In Immunology 2024, 15: 1414400. PMID: 39445014, PMCID: PMC11497637, DOI: 10.3389/fimmu.2024.1414400.Peer-Reviewed Original ResearchParameter optimizationMachine learning methodologyMachine learningComplex dataClustering outcomesLearning methodologyAssociated with immune disordersModified pipelineCell phenotypeImmune cell populationsDatasetBugsAutomated gatingOptimizationMachineImmunological datasetsImmune disordersScalabilityStable clustersCell populationsPipelineCellular changesCase studyCyTOFCyTOF dataSingle-nuclei RNA-seq reveals aberrant cell populations in restrictive allograft syndrome after lung transplantation
Leiber L, Christian L, Neubert L, Yilmaz H, Kamp J, Plucinski E, Welte T, Falk C, Kaminski N, Jonigk* D, Gottlieb* J, Schupp* J. Single-nuclei RNA-seq reveals aberrant cell populations in restrictive allograft syndrome after lung transplantation. 2024, oa985. DOI: 10.1183/13993003.congress-2024.oa985.Peer-Reviewed Original ResearchA phase Ib/II study of pacritinib, an interleukin 1 receptor associated kinase 1 (IRAK1) inhibitor, in patients (pts) with solid tumors harboring the 1q21.3 copy number amplification (CNA).
Lim J, Aau M, Yeong J, Goh B, Yong W, Soo R, Wong A, Tan D, Chee C, Sundar R, Jeyasekharan A, Wong C, Chen P, Liu H, Yu Q, Tam W, Lee S. A phase Ib/II study of pacritinib, an interleukin 1 receptor associated kinase 1 (IRAK1) inhibitor, in patients (pts) with solid tumors harboring the 1q21.3 copy number amplification (CNA). Journal Of Clinical Oncology 2024, 42: 43-43. DOI: 10.1200/jco.2024.42.23_suppl.43.Peer-Reviewed Original ResearchProgression-free survivalT cell populationsCD8+ T cell populationsCopy number amplificationInterleukin-1 receptor-associated kinase 1Solid tumorsTumor microenvironmentCell populationsDose levelsCD4+ T cell populationRecommended phase II dosePlasma cell-free DNAPeripheral blood mononuclear cells analysisSystemic immune modulationPhase II doseRefractory solid tumorsPhase Ib/II clinical trialDose-expansion cohortDendritic cell populationsMyeloid cell populationsTumor biopsy samplesImmune cell populationsDecreased tumor growthModulated immune cell populationsPreclinical animal models14 Natural killer cells have impaired cytotoxicity in advanced renal cell carcinoma
Moritz V, Xu W, Birch G, Meliki A, Bharadwaj M, Schindler N, Labaki C, Saliby R, Dinh K, Horst J, Sun M, Kashima S, Machaalani M, Lee G, Hurwitz M, McGregor B, Hirsch M, Shukla S, McDermott D, Signoretti S, Romee R, Choueiri T, Braun D. 14 Natural killer cells have impaired cytotoxicity in advanced renal cell carcinoma. The Oncologist 2024, 29: s7-s8. PMCID: PMC11301877, DOI: 10.1093/oncolo/oyae181.012.Peer-Reviewed Original ResearchNK cell phenotypeGene expression signaturesNK cell populationK562 target cellsNK cellsRenal cell carcinomaAdvanced ccRCCNK cell clustersLocalized ccRCCAnti-tumor activityNormal kidneyNatural killerCell carcinomaMarkers of tissue residencyAdvanced renal cell carcinomaProportion of NK cellsFunction of NK cellsExpression of cytotoxic genesTarget cellsNK cell dysfunctionTotal immune cellsNK cell subsetsCell phenotypeCell populationsCell renal cell carcinomaClonal cytopenia of undetermined significance: definitions, risk and therapeutic targets
Taborda C, Zeidan A, Mendez L. Clonal cytopenia of undetermined significance: definitions, risk and therapeutic targets. Frontiers In Hematology 2024, 3: 1419323. DOI: 10.3389/frhem.2024.1419323.Peer-Reviewed Original ResearchClonal hematopoiesis of indeterminate potentialClonal hematopoiesisClonal cytopeniaSomatic genetic alterationsTherapeutic targetStem/progenitor cell populationsRisk stratification toolBlood of individualsMyeloid malignanciesMyeloid neoplasmsHematologic malignanciesPotential therapeutic targetIndeterminate potentialRisk stratificationBlood countGenetic alterationsStratification toolClinical investigationNatural historyCell populationsCytopeniasMalignancyBloodRiskCytopenia(s1736-P: Exploring Intrinsic Features of Human Pancreatic a- and ß-Cell Physiology Using Pseudoislets
ROZO A, ROMAN J, QIN W, LIU C, NAJI A, KAESTNER K, HOSHI T, STOFFERS D, DOLIBA N. 1736-P: Exploring Intrinsic Features of Human Pancreatic a- and ß-Cell Physiology Using Pseudoislets. Diabetes 2024, 73 DOI: 10.2337/db24-1736-p.Peer-Reviewed Original ResearchB cell physiologyIslet cell typesCell typesOxygen consumption rateA cellsCa2+ fluxBaseline oxygen consumption rateIntrinsic cellular functionsGlucose-mediated inhibitionCellular functionsNative isletsPancreatic AEffect of glucoseMitochondrial functionResponse to glucoseAmino acidsRate of secretionGenetic interventionsPseudoisletsB cell aggregatesGlucose-induced inhibitionHuman APhysiologyCell populationsIsletsTert-expressing cells contribute to salivary gland homeostasis and tissue regeneration after radiation therapy
Guan L, Viswanathan V, Jiang Y, Vijayakumar S, Cao H, Zhao J, Colburg D, Neuhöfer P, Zhang Y, Wang J, Xu Y, Laseinde E, Hildebrand R, Rahman M, Frock R, Kong C, Beachy P, Artandi S, Le Q. Tert-expressing cells contribute to salivary gland homeostasis and tissue regeneration after radiation therapy. Genes & Development 2024, 38: 569-582. PMID: 38997156, PMCID: PMC11293384, DOI: 10.1101/gad.351577.124.Peer-Reviewed Original ResearchConceptsSubmandibular glandSalivary gland homeostasisProgenitor cellsGland homeostasisResponse to radiotherapyAdult submandibular glandCell survivalSalivary gland regenerationSelf-renewal capacityEnhanced proliferative activityRadiation therapyDuctal regionsRadiotherapyModulate cell survivalTelomerase-expressingGland regenerationProliferative activityMouse strainsTERT expressionCreERT2 recombinaseSalivary gland biologyRadiation exposureTERT locusIn vitro cultureCell populationsIn silico model development and optimization of in vitro lung cell population growth
Mostofinejad A, Romero D, Brinson D, Marin-Araujo A, Bazylak A, Waddell T, Haykal S, Karoubi G, Amon C. In silico model development and optimization of in vitro lung cell population growth. PLOS ONE 2024, 19: e0300902. PMID: 38748626, PMCID: PMC11095723, DOI: 10.1371/journal.pone.0300902.Peer-Reviewed Original ResearchCrosstalk between CD8+ T cells and mesenchymal stromal cells in intestine homeostasis and immunity
Chen Y, Sun H, Luo Z, Mei Y, Xu Z, Tan J, Xie Y, Li M, Xia J, Yang B, Su B. Crosstalk between CD8+ T cells and mesenchymal stromal cells in intestine homeostasis and immunity. Advances In Immunology 2024, 162: 23-58. PMID: 38866438, DOI: 10.1016/bs.ai.2024.02.001.Peer-Reviewed Original ResearchCD8+ T cellsMesenchymal stromal cell populationT cellsStromal cell populationsMHC II moleculesMesenchymal stromal cellsStromal cellsFunction of CD8+ T cellsCD103+ dendritic cellsMHC-IIIntestinal homeostasisCell populationsPotential pathophysiological impactGut-associated lymphoid tissueIgA+ plasma cellsDiseases of inflammationDead cell debrisTissue residencyDendritic cellsFood antigensIL-33Plasma cellsIntestinal toleranceLymphoid tissueImmunostimulatory agentsNeural-net-based cell deconvolution from DNA methylation reveals tumor microenvironment associated with cancer prognosis
Yasumizu Y, Hagiwara M, Umezu Y, Fuji H, Iwaisako K, Asagiri M, Uemoto S, Nakamura Y, Thul S, Ueyama A, Yokoi K, Tanemura A, Nose Y, Saito T, Wada H, Kakuda M, Kohara M, Nojima S, Morii E, Doki Y, Sakaguchi S, Ohkura N. Neural-net-based cell deconvolution from DNA methylation reveals tumor microenvironment associated with cancer prognosis. NAR Cancer 2024, 6: zcae022. PMID: 38751935, PMCID: PMC11094754, DOI: 10.1093/narcan/zcae022.Peer-Reviewed Original ResearchCell deconvolutionDNA methylation dataCancer prognosisTumor-infiltrating immune cellsFormalin-fixed paraffin-embedded sectionsImmune cell profilesAssociated with cancer prognosisImmune cell statusCell-free DNADNA methylationMethylation dataParaffin-embedded sectionsPeripheral bloodImmune cellsIntrahepatic cholangiocarcinoma samplesCell profilesFlow cytometryCell populationsClinical practiceClinical settingCholangiocarcinoma samplesCellular identityEpigenetic modificationsTumorPrognosisCharting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling
Cadinu P, Sivanathan K, Misra A, Xu R, Mangani D, Yang E, Rone J, Tooley K, Kye Y, Bod L, Geistlinger L, Lee T, Mertens R, Ono N, Wang G, Sanmarco L, Quintana F, Anderson A, Kuchroo V, Moffitt J, Nowarski R. Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling. Cell 2024, 187: 2010-2028.e30. PMID: 38569542, PMCID: PMC11017707, DOI: 10.1016/j.cell.2024.03.013.Peer-Reviewed Original ResearchConceptsMultiplexed error-robust fluorescence in situ hybridizationFluorescence in situ hybridizationSpatial organizationCell-cell interactionsDiverse cell populationsHealthy gutMouse colitis modelExpression profilesBiogeographyGutNon-immune cellsGut inflammationSpatial remodelingInflammation-associated fibroblastsTissue neighborhoodsInflammation-induced remodelingCell populationsFibroblastsImmune cellsCellsColitis modelUlcerative colitisFibroblastic originStage progressionExpression
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