2025
Single-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 functionDysregulationMonocytesLoss of GalNAc-T14 links O-glycosylation defects to alterations in B cell homing in IgA nephropathy
Prakash S, Steers N, Li Y, Sanchez-Rodriguez E, Verbitsky M, Robbins I, Simpson J, Pathak S, Raska M, Reily C, Ng A, Liang J, DeMaria N, Katiraei A, O'Stevens K, Fischman C, Shapiro S, Kodali S, McCutchan J, Park H, Eliby D, Delsante M, Allegri L, Fiaccadori E, Bodria M, Marasa M, Raveche E, Julian B, Uhlemann A, Kiryluk K, Zhang H, D'Agati V, Sanna-Cherchi S, Novak J, Gharavi A. Loss of GalNAc-T14 links O-glycosylation defects to alterations in B cell homing in IgA nephropathy. Journal Of Clinical Investigation 2025, 135: e181164. PMID: 40153534, PMCID: PMC12077892, DOI: 10.1172/jci181164.Peer-Reviewed Original ResearchConceptsO-glycosylationAberrant O-glycosylationIgA nephropathyMucosal immunityN-acetylgalactosaminyltransferaseElevated serum IgA levelsAdoptive-transfer experimentsB-cell homingSerum IgA levelsProtein O-glycosylationIgA-producing cellsGlomerular IgA depositionImmune-complex formationPathogenesis of IgANIgA1 hinge regionIgA1-producing cellsPeripheral bloodImpaired homingKidney injuryB cellsB lymphocytesIgA levelsLoF variantsIgA depositionGalNAc-T14Nanrilkefusp alfa (SOT101), an IL-15 receptor βγ superagonist, as a single agent or with anti-PD-1 in patients with advanced cancers
Champiat S, Garralda E, Galvao V, Cassier P, Gomez-Roca C, Korakis I, Grell P, Naing A, LoRusso P, Mikyskova R, Podzimkova N, Reinis M, Ouali K, Schoenenberger A, Kiemle-Kallee J, Tillmanns S, Sachse R, Moebius U, Spisek R, Bechard D, Jelinkova L, Adkins I, Marabelle A. Nanrilkefusp alfa (SOT101), an IL-15 receptor βγ superagonist, as a single agent or with anti-PD-1 in patients with advanced cancers. Cell Reports Medicine 2025, 6: 101967. PMID: 39933529, PMCID: PMC11866505, DOI: 10.1016/j.xcrm.2025.101967.Peer-Reviewed Original ResearchConceptsCD8<sup>+</sup> T cellsNatural killerT cellsAnti-programmed cell death protein 1Frequent treatment-emergent adverse eventsProportion of CD8<sup>+</sup> T cellsAnti-PD-1 pembrolizumabTreatment-emergent adverse eventsCell death protein 1Anti-PD-1Advanced/metastatic solid tumorsStimulated natural killerInjection site reactionsIL-15 receptorMouse tumor modelsPD-1NK cellsPeripheral bloodIL-15Safety profileSite reactionsSolid tumorsClinical efficacyAdverse eventsTumor modelTranscriptomic analysis reveals shared deregulated neutrophil responses in COVID-19 and idiopathic pulmonary fibrosis
Divolis G, Synolaki E, Tringidou R, Tzouvelekis A, Boumpas D, Skendros P, Galani I. Transcriptomic analysis reveals shared deregulated neutrophil responses in COVID-19 and idiopathic pulmonary fibrosis. Respiratory Research 2025, 26: 213. PMID: 40500689, PMCID: PMC12160113, DOI: 10.1186/s12931-025-03180-2.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosis patientsIdiopathic pulmonary fibrosisNeutrophil extracellular trapsPulmonary fibrosisIPF pathophysiologyPeripheral blood neutrophil countElevated peripheral blood neutrophil countsAcute respiratory distress syndromeCOVID-19 neutrophilsPeripheral blood of COVID-19 patientsLung biopsy specimensBlood of COVID-19 patientsRespiratory distress syndromeDeregulated immune responseNeutrophil extracellular trap formationBlood neutrophil countNeutrophil-driven pathologiesCOVID-19 pathogenesisCOVID-19 patientsLung biopsyBiopsy specimensDistress syndromePeripheral bloodNeutrophil countActivin/follistatin system
2024
Using Structure-Based Modeling to Identify Effective Drug Combinations in RAS-Mutant Acute Myeloid Leukemia
Jones L, Rukhlenko O, Dias T, Carmody C, Wynne K, Kholodenko B, Bond J. Using Structure-Based Modeling to Identify Effective Drug Combinations in RAS-Mutant Acute Myeloid Leukemia. Blood 2024, 144: 4161-4161. DOI: 10.1182/blood-2024-207308.Peer-Reviewed Original ResearchAcute myeloid leukemiaPatient-derived xenograftsCombination-treated miceInhibitor combinationsPeripheral bloodPhosphorylated ERKBone marrowRAS pathway activationSpleen weightMyeloid leukemiaAML patient-derived xenograftDrug combinationsVehicle controlSingle agentHuman CD45+ cellsPre-clinical mouse modelPediatric acute myeloid leukemiaAssociated with poor outcomesHigh-risk patient groupsMedian spleen weightSB-treated micePreclinical in vivo modelsCD45+ cellsLateral tail veinPathway activationDexamethasone Targets E2F4 to Induce Erythroid Progenitor Renewal
Papoin J, Schulz V, Khan F, Barnes B, Lipton J, Steiner L, Narla M, Gallagher P, Blanc L. Dexamethasone Targets E2F4 to Induce Erythroid Progenitor Renewal. Blood 2024, 144: 1076. DOI: 10.1182/blood-2024-211687.Peer-Reviewed Original ResearchDiamond-Blackfan anemiaCD34+ cellsErythroid progenitorsSteroid responsivenessExpression of E2F4Peripheral bloodBone marrowE2F4 expressionDEX treatmentCultured CD34+ cellsInherited bone marrow failure syndromeMechanisms of steroid responseSide effectsBone marrow failure syndromesDiamond-Blackfan anemia patientsBone marrow erythroid progenitorsIncreased expressionMechanisms of corticosteroid actionAssociated with side effectsIncreased risk of infectionMarrow failure syndromesResponse to steroidsGene promoterSerum-free culture systemMarrow erythroid progenitorsLandscape of Immune Cell States and Ecosystems in Patients with Myelodysplastic Syndrome to Refine Prognostic Assessment and Predict Treatment Response. a Study By i4MDS Consortium
Riva E, Calvi M, Zampini M, Dall'Olio L, Merlotti A, Russo A, Maggioni G, Orlandi L, Frigo A, Ficara F, Crisafulli L, Sauta E, D'Amico S, Lugli E, Campagna A, Ubezio M, Tentori C, Todisco G, Lanino L, Buizza A, Ventura D, Pinocchio N, Saba E, Santoro A, Santini V, van de Loosdrecht A, Komrokji R, Garcia-Manero G, Fenaux P, Ades L, Platzbecker U, Haferlach T, Almeida A, Zeidan A, Kordasti S, Remondini D, Castellani G, Di Vito C, Mavilio D, Della Porta M. Landscape of Immune Cell States and Ecosystems in Patients with Myelodysplastic Syndrome to Refine Prognostic Assessment and Predict Treatment Response. a Study By i4MDS Consortium. Blood 2024, 144: 665-665. DOI: 10.1182/blood-2024-200184.Peer-Reviewed Original ResearchMyelodysplastic syndromeImmune dysfunctionClinical work-upIPSS-MHypomethylating agentsBone marrowImmune ecosystemNatural killerNK cellsImmune monitoringPeripheral bloodT cellsAntibody panelClinical heterogeneity of myelodysplastic syndromesPatients treated with hypomethylating agentsCohort of MDS patientsLevel of immune dysfunctionRisk of leukemic transformationResponse to hypomethylating agentsHeterogeneity of myelodysplastic syndromesMulti-color flow cytometryWork-up of patientsClinical work-up of patientsImmune monitoring approachesMDS microenvironmentCffDNA screening for Niemann–pick disease, type C1: a case series
Lau S, Fawaz R, Rigobello R, Bawazeer S, Alajaji N, Faqeih E, Li Y, Feng Y, Xia F, Eng C, Abedalthagafi M. CffDNA screening for Niemann–pick disease, type C1: a case series. Frontiers In Medicine 2024, 11: 1390693. PMID: 39161410, PMCID: PMC11330825, DOI: 10.3389/fmed.2024.1390693.Peer-Reviewed Original ResearchNext-generation sequencingInvasive diagnostic testsCffDNA screeningNiemann-Pick diseaseCustom data analysis pipelineAmplicon next-generation sequencingAmplicon-based next-generation sequencingDisease-causing variantsType C1Biallelic pathogenic variantsData analysis pipelinesCell-free fetal DNADetect chromosomal abnormalitiesMaternal peripheral bloodDiagnostic testsWeeks of gestationNPC1 geneHigh-risk pregnanciesPathogenic variantsAnalysis pipelineFamilial variantFetal DNAProgressive neurodegenerationChromosomal abnormalitiesPeripheral bloodCNS cell-derived exosome signatures as blood-based biomarkers of neurodegenerative diseases
Park C, Weerakkody J, Schneider R, Miao S, Pitt D. CNS cell-derived exosome signatures as blood-based biomarkers of neurodegenerative diseases. Frontiers In Neuroscience 2024, 18: 1426700. PMID: 38966760, PMCID: PMC11222337, DOI: 10.3389/fnins.2024.1426700.Peer-Reviewed Original ResearchNeurodegenerative diseasesSubtype of extracellular vesiclesDisease-related processesDisease-associated changesCentral nervous systemBlood-based proteinsBiomarkers of neurodegenerative diseasesBlood-brain barrierCell typesExosome populationMolecular cargoExtracellular vesiclesCell of originRNA biomarkersExosome isolationTranslation to clinical useCell-derived exosomesLack of standardized methodologyMolecular contentExosomesBlood-based biomarkersPeripheral bloodCellsExosome signatureMolecular biomarkersUnilateral focal palmoplantar keratoderma associated with a postzygotic variant in PIK3CA and activation of the PI3K/AKT/mTOR pathway.
Gong Z, Peng S, Wang H, Jiang X, Ke X, Lin Z. Unilateral focal palmoplantar keratoderma associated with a postzygotic variant in PIK3CA and activation of the PI3K/AKT/mTOR pathway. European Journal Of Dermatology 2024, 34: 287-293. PMID: 39015962, DOI: 10.1684/ejd.2024.4704.Peer-Reviewed Original ResearchConceptsFocal palmoplantar keratodermaLaser capture microdissectionIdentified missense variantsPalmoplantar keratodermaWhole-exome sequencingMissense variantsGenomic DNASomatic variantsGenetic basisSanger sequencingMolecular dockingPostzygotic variantsBiological processesPI3K/AKT/mTOR pathwayPhenotypic heterogeneityEpidermal nevusPatient's peripheral bloodCongenital overgrowth disorderVariantsPIK3CASequencePeripheral bloodPI3K/Akt/mTOR signalingAffected epidermisOvergrowth disorderResults from phase 1a/1b analyses of TTX-080, a first in class HLA-G antagonist, in combination with cetuximab in patients (pts) with metastatic colorectal cancer and head and neck squamous cell carcinoma.
Ulahannan S, Marron T, Park H, Kaczmar J, Stephenson R, Lakhani N, Durm G, Grewal J, El-Khoueiry A, Luke J, Beers C, Murugappan S, LoRusso P, Adkins D, Hecht J. Results from phase 1a/1b analyses of TTX-080, a first in class HLA-G antagonist, in combination with cetuximab in patients (pts) with metastatic colorectal cancer and head and neck squamous cell carcinoma. Journal Of Clinical Oncology 2024, 42: 2524-2524. DOI: 10.1200/jco.2024.42.16_suppl.2524.Peer-Reviewed Original ResearchHead and neck squamous cell carcinomaMetastatic colorectal cancerNeck squamous cell carcinomaSquamous cell carcinomaPreliminary efficacy dataCell carcinomaColorectal cancerEfficacy dataSolid tumor cohortTreatment-related AEsImmune cell changesAnti-tumor activityStandard of careRandomized Controlled StudyDose escalationEscalating dosesHLA-G.Peripheral bloodTumor cohortsSolid tumorsDecreased appetiteAST increaseBlood samplesCell changesQ3wReshaping 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-riskA Monocyte-specific Gene-signature Predicts Outcomes in Patients With Idiopathic Pulmonary Fibrosis and Is Reproducible in Peripheral Blood, Bronchoalveolar Lavage, and Lung Tissue
Karampitsakos T, Tourki B, Juan-Guardela B, Perrot C, Marlin K, Arsenault A, Binder H, Wuyts W, Rottoli P, Prasse A, Tzouvelekis A, Restrepo Jaramillo R, Qureshi M, Patel K, Bandyopadhyay D, Kaminski N, Herazo-Maya J. A Monocyte-specific Gene-signature Predicts Outcomes in Patients With Idiopathic Pulmonary Fibrosis and Is Reproducible in Peripheral Blood, Bronchoalveolar Lavage, and Lung Tissue. 2024, a2860-a2860. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a2860.Peer-Reviewed Original ResearchNeural-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 modificationsTumorPrognosisEvidence for C-Peptide as a Validated Surrogate to Predict Clinical Benefits in Trials of Disease-Modifying Therapies for Type 1 Diabetes.
Latres E, Greenbaum C, Oyaski M, Dayan C, Colhoun H, Lachin J, Skyler J, Rickels M, Ahmed S, Dutta S, Herold K, Marinac M. Evidence for C-Peptide as a Validated Surrogate to Predict Clinical Benefits in Trials of Disease-Modifying Therapies for Type 1 Diabetes. Diabetes 2024, 73: 823-833. PMID: 38349844, DOI: 10.2337/dbi23-0012.Peer-Reviewed Original ResearchBeta cell functionType 1 diabetesMeasures of beta cell functionDisease-modifying therapiesC-peptideTrials of disease-modifying therapiesClinical benefitCell functionDestruction of pancreatic beta cellsStimulated C-peptideC-peptide levelsEnd-organ complicationsProspective cohort studyAssociated with protectionEnd-organ complications of diabetesChronic autoimmune diseaseClinically Meaningful OutcomesClinical outcome measuresComplications of diabetesClinical trials of disease-modifying therapiesBeta cell preservationDemonstration of efficacyPancreatic beta cellsPeripheral bloodAutoimmune diseases
2023
Aging gene signature of memory CD8+ T cells is associated with neurocognitive functioning in Alzheimer’s disease
Young J, Park H, Kim M, Par-Young J, Bartlett H, Kim H, Unlu S, Osmani L, Shin M, Bucala R, van Dyck C, Allore H, Mecca A, You S, Kang I. Aging gene signature of memory CD8+ T cells is associated with neurocognitive functioning in Alzheimer’s disease. Immunity & Ageing 2023, 20: 71. PMID: 38042785, PMCID: PMC10693128, DOI: 10.1186/s12979-023-00396-y.Peer-Reviewed Original ResearchPeripheral bloodT cellsAlzheimer's diseaseEM CD8Memory CD8Gene signatureAge-related immune changesIL-7 receptor alphaEffector memory CD8Strong risk factorT cell expansionAD genesAge-associated expansionImmune changesRisk factorsCD8Dementia patientsIL-7RNeuropsychological testingReceptor alphaNeurocognitive functionRT-qPCR resultsDisease severityPatientsNormal persons2368. SARS-CoV-2 mRNA vaccination induces B cell immunity in the tonsils and adenoids of children
Xu Q, Mudd P, Behzadpour H, Bellusci L, Grubbs G, Pourhashemi S, Tang J, Liu C, Newman D, Shi L, Milanez-Almeida P, Kardava L, Tsang J, Moir S, Khurana S, Schwartzberg P, Manthiram K. 2368. SARS-CoV-2 mRNA vaccination induces B cell immunity in the tonsils and adenoids of children. Open Forum Infectious Diseases 2023, 10: ofad500.1989. PMCID: PMC10677082, DOI: 10.1093/ofid/ofad500.1989.Peer-Reviewed Original ResearchSARS-CoV-2-specific B cellsMemory B cellsB cellsAdenoids of childrenMRNA vaccinesVaccinated subjectsPeripheral bloodInfected subjectsUpper respiratory tract lymphoid tissueSARS-CoV-2IgA+ memory B cellsSARS-CoV-2 mRNA vaccinesGerminal center B cellsRobust adaptive immune responsesPost-vaccinationCOVID-19 mRNA vaccinesB-cell phenotypeB cell immunityAdaptive immune responsesImmunity to SARS-CoV-2SARS-CoV-2 infectionPost-infectionLymphoid tissueAdenoidsMucosal IgAMaternal CXCR4 deletion results in placental defects and pregnancy loss mediated by immune dysregulation
Lyu F, Burzynski C, Fang Y, Tal A, Chen A, Kisa J, Agrawal K, Kluger Y, Taylor H, Tal R. Maternal CXCR4 deletion results in placental defects and pregnancy loss mediated by immune dysregulation. JCI Insight 2023, 8: e172216. PMID: 37815869, PMCID: PMC10721256, DOI: 10.1172/jci.insight.172216.Peer-Reviewed Original ResearchConceptsCXCR4-deficient micePlacental vascular developmentNK cellsCxcr4 deletionNormal placental vascular developmentPlacental developmentNK cell dysfunctionNK cell expressionNK cell infiltrationNK cell functionRole of CXCR4Cell functionMaternal-fetal interfaceImmune cell functionEarly placental developmentWt CXCR4Immune dysregulationVascular developmentGiant cell layerImmune toleranceCXCR4 expressionPeripheral bloodPregnancy failureCell infiltrationPregnancy lossLow Dose Total Body Irradiation Improves CD19 CAR-T Expansion, Persistence, and Trafficking, Leading to Enhanced Efficacy in Large B-Cell Lymphoma
Alhomoud M, Foley M, Sugita M, Yamazaki T, Martinez L, Yamshon S, Gomez-Arteaga A, Pagnini P, Shore T, Boyer O, Brentjens R, Van Besien K, Galluzzi L, Formenti S, Martinet J, Guzman M. Low Dose Total Body Irradiation Improves CD19 CAR-T Expansion, Persistence, and Trafficking, Leading to Enhanced Efficacy in Large B-Cell Lymphoma. Blood 2023, 142: 1016. DOI: 10.1182/blood-2023-185216.Peer-Reviewed Original ResearchLow-dose total body irradiationLarge B-cell lymphomaDose total body irradiationTotal body irradiationSyngeneic mouse modelB-cell lymphomaComplete remissionDays post treatmentExpression of FasBody irradiationSecond dosePeripheral bloodGy radiationMouse modelAnti-CD19 Chimeric Antigen Receptor T CellsA20 cellsChimeric antigen receptor T cellsAntigen receptor T cellsBALB/c miceB-cell recoveryAdditional survival benefitB-cell aplasiaReceptor T cellsImmunosuppressive tumor microenvironmentBone marrow aspirateImpact of Mutational Status on Clinical Response to Imetelstat in Patients with Lower-Risk Myelodysplastic Syndromes in the IMerge Phase 3 Study
Santini V, Zeidan A, Fenaux P, Madanat Y, Berry T, Feller F, Sun L, Xia Q, Wan Y, Huang F, Savona M, Platzbecker U. Impact of Mutational Status on Clinical Response to Imetelstat in Patients with Lower-Risk Myelodysplastic Syndromes in the IMerge Phase 3 Study. Blood 2023, 142: 4603. DOI: 10.1182/blood-2023-179378.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesPlacebo groupTransfusion independenceTI ratesHot spot mutationsPoor prognosisMyelodysplastic syndromeRed blood cell transfusion independenceASXL1 mutationsErythropoiesis-stimulating agentsPhase 3 studyStudy of patientsTI responsesPresence of mutationsSpecific mutationsClinical responseStudy entryClinical efficacyClinical benefitPeripheral bloodMutation subgroupsDNMT3A mutationsEpigenetic modifiersPatientsRUNX1 mutations
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