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 compartmentsDeathDeletion of sphingosine 1-phosphate receptor 1 in myeloid cells reduces hepatic inflammatory macrophages and attenuates MASH
Parthasarathy G, Venkatesan N, Sidhu G, Song M, Liao C, Barrow F, Mauer A, Sehrawat T, Nakao Y, Daniel P, Dasgupta D, Pavelko K, Revelo X, Malhi H. Deletion of sphingosine 1-phosphate receptor 1 in myeloid cells reduces hepatic inflammatory macrophages and attenuates MASH. Hepatology Communications 2025, 9: e0613. PMID: 39899672, DOI: 10.1097/hc9.0000000000000613.Peer-Reviewed Original ResearchConceptsMyeloid cellsMonocyte-derived macrophagesHigh-fatLiver injuryProinflammatory monocyte-derived macrophagesReceptor 1Cell-specific knockout miceMass cytometryT cell subsetsSphingosine 1-phosphate receptor 1Cardiometabolic risk factorsS1P receptor 1Accumulation of monocyte-derived macrophagesImmune cell typesWild-typeLiver inflammatory infiltrationGene ontology pathway analysisWild-type controlsDevelopment of steatohepatitisSphingosine 1-phosphateMitogen-activated protein kinase pathwayT cellsIntrahepatic macrophagesInflammatory infiltrateKnockout mice
2024
Molecular MRI of T-cell immune response to cryoablation in immunologically hot vs. cold hepatocellular carcinoma
Santana J, Shewarega A, Nam D, Duncan J, Madoff D, Hyder F, Coman D, Chapiro J. Molecular MRI of T-cell immune response to cryoablation in immunologically hot vs. cold hepatocellular carcinoma. JHEP Reports 2024, 7: 101294. PMID: 40028344, PMCID: PMC11870164, DOI: 10.1016/j.jhepr.2024.101294.Peer-Reviewed Original ResearchT cell infiltrationHepatocellular carcinomaRadiological-pathological correlationImaging mass cytometryImmune responseT1-weighted MRITumor-infiltrating CD8+ T lymphocytesAnti-tumor immune responseCD8+ T lymphocytesIncreased T lymphocyte infiltrationImaging biomarkersNon-immunogenic tumorsSystemic lymph nodesT lymphocyte infiltrationMurine tumor modelsImmune cell typesLocal tumor therapyPrimary liver cancerNon-invasive imaging biomarkerTesla MRI scannerInduce liver cirrhosisImmunogenic tumorsLocoregional therapySystemic immunotherapyHCC lesionsA spatial expression atlas of the adult human proximal small intestine
Harnik Y, Yakubovsky O, Hoefflin R, Novoselsky R, Bahar Halpern K, Barkai T, Korem Kohanim Y, Egozi A, Golani O, Addadi Y, Kedmi M, Keidar Haran T, Levin Y, Savidor A, Keren-Shaul H, Mayer C, Pencovich N, Pery R, Shouval D, Tirosh I, Nachmany I, Itzkovitz S. A spatial expression atlas of the adult human proximal small intestine. Nature 2024, 632: 1101-1109. PMID: 39112711, DOI: 10.1038/s41586-024-07793-3.Peer-Reviewed Original ResearchConceptsExpression atlasSingle-molecule fluorescence in situ hybridizationLipid droplet assemblyAdult human gutFluorescence in situ hybridizationHuman proximal small intestineHuman small intestineHuman gutSpatial proteomicsProximal small intestineTip cellsGene expressionSmall intestineIron uptakeSpatial transcriptomicsVillus tip cellsImmune cell typesMouse small intestineCell typesDroplet assemblyImmunosuppressive rolePro-immunogenicAdult human small intestineT cellsZonated expressioniGATE analysis improves the interpretability of single-cell immune landscape of influenza infection
Hill B, Zak A, Raja S, Bugada L, Rizvi S, Roslan S, Nguyen H, Chen J, Jiang H, Ono A, Goldstein D, Wen F. iGATE analysis improves the interpretability of single-cell immune landscape of influenza infection. JCI Insight 2024, 9: e172140. PMID: 38814732, PMCID: PMC11383363, DOI: 10.1172/jci.insight.172140.Peer-Reviewed Original ResearchInfluenza infectionImmune cell typesCourse of influenza infectionDefective T cell responsesSurvival of C57BL/6 miceCell typesDecreased IL-10 expressionEffect of host genetic backgroundT cell responsesGenetic backgroundTime-of-flight (CyTOFIL-10 expressionInflammatory cell typesCells in silicoHost genetic backgroundC57BL/6 miceAged miceMouse lungHost genotypeInfection susceptibilityHost factorsEffects of ageMiceHealth burdenInfectionTh2 Cells Are Associated with Tumor Recurrence Following Radiation
Abdelhakiem M, Bao R, Pifer P, Molkentine D, Molkentine J, Hefner A, Beadle B, Heymach J, Luke J, Ferris R, Pickering C, Wang J, Patel R, Skinner H. Th2 Cells Are Associated with Tumor Recurrence Following Radiation. Cancers 2024, 16: 1586. PMID: 38672668, PMCID: PMC11049347, DOI: 10.3390/cancers16081586.Peer-Reviewed Original ResearchHead and neck squamous cell carcinomaLocoregional recurrenceValidation cohortTh2 infiltrationDiscovery cohortTh2 cellsTreatment of multiple solid tumorsAssociated with locoregional recurrenceNeck squamous cell carcinomaAssociated with tumor recurrencePrognostic immune biomarkersAntitumor immune responseTumor immune infiltrationSquamous cell carcinomaMultiple solid tumorsIndependent validation cohortResponse to radiationImmune cell typesMechanism of radiation resistanceAssociated with outcomeAdjuvant radiationTumor recurrenceHNSCC tumorsCell carcinomaImmune infiltrationComputationally inferred cell-type specific epigenome-wide DNA methylation analysis unveils distinct methylation patterns among immune cells for HIV infection in three cohorts
Zhang X, Hu Y, Vandenhoudt R, Yan C, Marconi V, Cohen M, Wang Z, Justice A, Aouizerat B, Xu K. Computationally inferred cell-type specific epigenome-wide DNA methylation analysis unveils distinct methylation patterns among immune cells for HIV infection in three cohorts. PLOS Pathogens 2024, 20: e1012063. PMID: 38466776, PMCID: PMC10957090, DOI: 10.1371/journal.ppat.1012063.Peer-Reviewed Original ResearchCD4+ T cellsEpigenome-wide association studiesPeripheral blood mononuclear cellsHIV infectionHIV pathogenesisT cellsCpG sitesNatural killer (NK) cellsCell typesAssociated with HIV infectionCD8+ T cellsMethylation patternsCpG methylationDNA methylationEpigenome-wide DNA methylation analysisBlood mononuclear cellsImmune cell typesDifferentially methylated CpG sitesUnique CpG sitesDifferential CpG methylationDNA methylation analysisSignificant CpG sitesArray-based methodsGene set enrichment analysisComputational deconvolution methodsCombined Genetic Association and Differed Expression Analysis of UBE2L3 Uncovers a Genetic Regulatory Role of (Immuno)proteasome in IgA Nephropathy
Xu L, Gan T, Li Y, Chen P, Shi S, Liu L, Lv J, Zhang H, Zhou X. Combined Genetic Association and Differed Expression Analysis of UBE2L3 Uncovers a Genetic Regulatory Role of (Immuno)proteasome in IgA Nephropathy. Kidney Diseases 2024, 10: 167-180. PMID: 38835407, PMCID: PMC11149991, DOI: 10.1159/000537987.Peer-Reviewed Original ResearchGd-IgA1IgA nephropathyHealthy controlsProteasome subunitsLevels of Gd-IgA1Genetic associationPeripheral blood mononuclear cellsExpression levelsEnd-stage renal diseaseSusceptibility to IgANBlood mononuclear cellsGd-IgA1 productionImmune cell typesBlood mRNA levelsFollow-up dataGalactose-deficient IgA1Cell typesUbiquitin-proteasome systemProcess of glycosylationPathogenesis of IgANAssociation of variantsDevelopment of IgANHigher proteinuriaLow eGFRHighest expression levelLAG-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 typesClinicCellsTherapyNeutrophils in Physiology and Pathology
Aroca-Crevillén A, Vicanolo T, Ovadia S, Hidalgo A. Neutrophils in Physiology and Pathology. Annual Review Of Pathology Mechanisms Of Disease 2024, 19: 227-259. PMID: 38265879, PMCID: PMC11060889, DOI: 10.1146/annurev-pathmechdis-051222-015009.Peer-Reviewed Original Research
2023
Machine learning-based cluster analysis of immune cell subtypes and breast cancer survival
Wang Z, Katsaros D, Wang J, Biglio N, Hernandez B, Fei P, Lu L, Risch H, Yu H. Machine learning-based cluster analysis of immune cell subtypes and breast cancer survival. Scientific Reports 2023, 13: 18962. PMID: 37923775, PMCID: PMC10624674, DOI: 10.1038/s41598-023-45932-4.Peer-Reviewed Original ResearchConceptsImmune cell clustersT cellsHost immunityImmune cellsUnsupervised hierarchical clusteringImmune responseCD8-positive T cellsMemory CD4 T cellsCox regression survival analysisRegulatory T cellsPositive T cellsCD4 T cellsDifferent immune cellsDistinct immune responsesBreast cancer survivalImmune cell subtypesMemory B cellsImmune cell typesRegression survival analysisCell clustersBreast cancer progressionT cell receptor signalingCytokine stormOverall survivalFavorable survivalEarly cellular and molecular signatures correlate with severity of West Nile virus infection
Lee H, Zhao Y, Fleming I, Mehta S, Wang X, Vander Wyk B, Ronca S, Kang H, Chou C, Fatou B, Smolen K, Levy O, Clish C, Xavier R, Steen H, Hafler D, Love J, Shalek A, Guan L, Murray K, Kleinstein S, Montgomery R. Early cellular and molecular signatures correlate with severity of West Nile virus infection. IScience 2023, 26: 108387. PMID: 38047068, PMCID: PMC10692672, DOI: 10.1016/j.isci.2023.108387.Peer-Reviewed Original ResearchWest Nile virusEffective anti-viral responseInnate immune cell typesWest Nile virus infectionPro-inflammatory markersAcute time pointsImmune cell typesAnti-viral responseMolecular signaturesHost cellular activitiesAcute infectionAsymptomatic donorsPeripheral bloodSevere infectionsVirus infectionImmune responseSevere casesCell activityIll individualsSerum proteomicsInfectionInfection severityHigh expressionTime pointsNile virusCharacterization of papillary and clear cell renal cell carcinoma through imaging mass cytometry reveals distinct immunologic profiles
Govindarajan A, Salgia N, Li H, Castro D, Mirzapoiazova T, Armstrong B, Zhao D, Mercier B, Dizman N, Chawla N, Zengin Z, Meza L, Tripathi N, Sayegh N, Chehrazi-Raffle A, Tripathi A, Pal S. Characterization of papillary and clear cell renal cell carcinoma through imaging mass cytometry reveals distinct immunologic profiles. Frontiers In Immunology 2023, 14: 1182581. PMID: 37638025, PMCID: PMC10457014, DOI: 10.3389/fimmu.2023.1182581.Peer-Reviewed Original ResearchConceptsClear cell renal cell carcinomaPapillary renal cell carcinomaRenal cell carcinomaCell renal cell carcinomaCell carcinomaT cellsTumor microenvironmentPRCC cohortCcRCC cohortCcRCC patientsMain immune cell typesDistinct immunologic profileRCC histological subtypesMedian overall survivalProportion of CD4Baseline tumor tissueImmune cell populationsSubtypes of RCCImmune cell typesMass cytometry analysisCross-validate findingsSignificant differencesFFPE samplesMacrophage compositionTME compartmentsCell-matrix interactions control biliary organoid polarity, architecture, and differentiation
Fiorotto R, Mariotti V, Taleb S, Zehra S, Nguyen M, Amenduni M, Strazzabosco M. Cell-matrix interactions control biliary organoid polarity, architecture, and differentiation. Hepatology Communications 2023, 7: e0094. PMID: 36972396, PMCID: PMC10503667, DOI: 10.1097/hc9.0000000000000094.Peer-Reviewed Original ResearchConceptsBiliary organoidsNovel organoid modelImmune cell typesOrganotypic culture systemProinflammatory chemokinesStem cell featuresBiliary epitheliumExtracellular matrixEpithelial permeabilityImportant causeBile acidsBiliary differentiationBile transportHuman liverOrganoid modelsDisease modelsCholangiopathyCell featuresTight junctionsLiverCell typesInternal lumenOrganoidsSingle-cell transcriptomicsPathogenic bacteria
2022
Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines
Godoy-Tena G, Barmada A, Morante-Palacios O, de la Calle-Fabregat C, Martins-Ferreira R, Ferreté-Bonastre A, Ciudad L, Ruiz-Sanmartín A, Martínez-Gallo M, Ferrer R, Ruiz-Rodriguez J, Rodríguez-Ubreva J, Vento-Tormo R, Ballestar E. Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines. Genome Medicine 2022, 14: 134. PMID: 36443794, PMCID: PMC9706884, DOI: 10.1186/s13073-022-01137-4.Peer-Reviewed Original ResearchConceptsDNA methylation alterationsSevere COVID-19 patientsInterferon-related genesCOVID-19 patientsCell typesMethylation alterationsMyeloid differentiationSingle-cell transcriptomesSingle-cell transcriptomicsDNA methylation changesGene expression changesPeripheral blood monocytesImmune cell typesMethylationEPIC BeadChip arraySpecific DNA methylation alterationsTranscriptional reprogrammingDNA methylomeTranscriptomic reprogrammingDNA methylationInflammatory cytokinesMethylation changesEpigenetic alterationsBlood monocytesExpression changesBeadChip arraySpatial profiling of chromatin accessibility in mouse and human tissues
Deng Y, Bartosovic M, Ma S, Zhang D, Kukanja P, Xiao Y, Su G, Liu Y, Qin X, Rosoklija GB, Dwork AJ, Mann JJ, Xu ML, Halene S, Craft JE, Leong KW, Boldrini M, Castelo-Branco G, Fan R. Spatial profiling of chromatin accessibility in mouse and human tissues. Nature 2022, 609: 375-383. PMID: 35978191, PMCID: PMC9452302, DOI: 10.1038/s41586-022-05094-1.Peer-Reviewed Original ResearchConceptsChromatin accessibilityATAC-seqSpecific epigenetic landscapesChromatin accessibility profilingCell fate decisionsEpigenetic informationEpigenetic landscapeGenome scaleFate decisionsAccessible genomeCell identityEpigenetic underpinningsNext-generation sequencingGene regulatorsCell statesMouse embryosSpatial biologySpatial transcriptomicsCell typesCellular levelImmune cell typesDistinct organizationHuman tissuesProfilingSpatial profilingGenome Engineering for Next-Generation Cellular Immunotherapies
Park JJ, Lee KAV, Lam SZ, Tang K, Chen S. Genome Engineering for Next-Generation Cellular Immunotherapies. Biochemistry 2022, 62: 3455-3464. PMID: 35930700, PMCID: PMC11320893, DOI: 10.1021/acs.biochem.2c00340.Peer-Reviewed Original ResearchConceptsGenome engineeringCellular immunotherapySynthetic biology approachesKnockout of genesGenome engineering approachesGenetic screening approachCell therapyNK cell therapyCAR-NK cellsBiology approachHost-graft interactionsNovel target discoveryLong-term persistenceImmune cell typesCRISPR-CasFuture therapeutic developmentTarget discoveryGenetic modificationCell typesAllogeneic contextTumor effect
2021
Targeting the CSF1/CSF1R axis is a potential treatment strategy for malignant meningiomas
Yeung J, Yaghoobi V, Miyagishima D, Vesely MD, Zhang T, Badri T, Nassar A, Han X, Sanmamed MF, Youngblood M, Peyre M, Kalamarides M, Rimm DL, Gunel M, Chen L. Targeting the CSF1/CSF1R axis is a potential treatment strategy for malignant meningiomas. Neuro-Oncology 2021, 23: 1922-1935. PMID: 33914067, PMCID: PMC8563319, DOI: 10.1093/neuonc/noab075.Peer-Reviewed Original ResearchConceptsColony-stimulating factor-1Myeloid cellsMalignant meningiomasTumor microenvironmentCSF1/CSF1RRNA-seqRNA sequencingHuman meningiomasImmune subsetsGene expressionT cellsTreatment strategiesNormalization cancer immunotherapyImportant regulatorCell typesNovel immunocompetent murine modelDeath ligand 1 (PD-L1) expressionCell death receptor-1Immunosuppressive myeloid cellsDeath receptor-1Ligand 1 expressionFactor 1Immune cell typesImmunocompetent murine modelEffective treatment strategiesChapter 9 Mechanism of glucocorticoid action in immunology—Basic concepts
Wood M, Whirledge S. Chapter 9 Mechanism of glucocorticoid action in immunology—Basic concepts. 2021, 147-170. DOI: 10.1016/b978-0-12-818508-7.00020-8.Peer-Reviewed Original ResearchGlucocorticoid receptorEpigenetic modificationsPosttranslational modificationsTranscription factorsDNA bindingTissue-specific immune responsesOverall physiologyCell typesGlucocorticoid-mediated effectsNuclear receptorsImmune cell typesFundamental processesReceptor isoformsLevels of hormonesRelative expressionReceptor actionReproductive systemChapter 9 MechanismsGlucocorticoid bioavailabilityAutoimmune diseasesGlucocorticoid actionImmune responseFetal developmentCo-FactorImmune system
2020
Regulation and characterization of tumor-infiltrating immune cells in breast cancer
Dai Q, Wu W, Amei A, Yan X, Lu L, Wang Z. Regulation and characterization of tumor-infiltrating immune cells in breast cancer. International Immunopharmacology 2020, 90: 107167. PMID: 33223469, PMCID: PMC7855363, DOI: 10.1016/j.intimp.2020.107167.Peer-Reviewed Original ResearchConceptsTumor-infiltrating immune cellsT cell activation statusImmune cellsCell activation statusT cell activationPatient survivalM2 macrophagesT cellsBreast cancerCell activationT cell peripheral toleranceTumor-infiltrating B cellsMultivariate Cox regression modelActivation statusBreast cancer patient survivalEffector T cellsT cell subsetsBreast cancer patientsImmune cell infiltrationAbundant plasma cellsCox regression modelKaplan-Meier survivalImmune cell typesMolecular pathwaysCancer patient survival
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