2025
Cerebrospinal fluid immune phenotyping reveals distinct immunotypes of myalgic encephalomyelitis/chronic fatigue syndrome.
Bastos V, Greene K, Tabachnikova A, Bhattacharjee B, Sjögren P, Bertilson B, Reifert J, Zhang M, Kamath K, Shon J, Gehlhausen J, Guan L, VanElzakker M, Proal A, Bragée B, Iwasaki A. Cerebrospinal fluid immune phenotyping reveals distinct immunotypes of myalgic encephalomyelitis/chronic fatigue syndrome. The Journal Of Immunology 2025 PMID: 40373264, DOI: 10.1093/jimmun/vkaf087.Peer-Reviewed Original ResearchMyalgic encephalomyelitis/chronic fatigue syndromeCerebrospinal fluidImmune phenotypeFatigue syndromeMatched healthy control subjectsAssessed plasma samplesMultiplex analysis of cytokinesHealthy control subjectsAnalysis of cerebrospinal fluidAnalysis of cytokinesTreatment developmentClinical presentationSymptom presentationMultiorgan diseaseInflammatory profileControl subjectsPathophysiological mechanismsMatrix metalloproteinase profilesDisease subgroupsME/CFS participantsClinical questionnaireMatrix metalloproteinasesMetalloproteinase profilesHigh-throughput microarrayPlasma samplesImpact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID
Grady C, Bhattacharjee B, Silva J, Jaycox J, Lee L, Silva Monteiro V, Sawano M, Massey D, Caraballo C, Gehlhausen J, Tabachnikova A, Mao T, Lucas C, Peña-Hernandez M, Xu L, Tzeng T, Takahashi T, Herrin J, Güthe D, Akrami A, Assaf G, Davis H, Harris K, McCorkell L, Schulz W, Griffin D, Wei H, Ring A, Guan L, Dela Cruz C, Krumholz H, Iwasaki A. Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID. Communications Medicine 2025, 5: 163. PMID: 40346201, PMCID: PMC12064684, DOI: 10.1038/s43856-025-00829-3.Peer-Reviewed Original ResearchSpike protein-specific IgGProtein-specific IgGSelf-antigensImmune response to COVID-19 vaccinationCOVID-19 vaccineAntibody responseResponse to COVID-19 vaccinationT cell expansionSARS-CoV-2-specific antibody responsesAssociated with no improvementLong COVIDAssociated with symptom improvementChest painCirculating cytokinesImmune phenotypeProspective studyImmune featuresTransient improvementPrimary seriesVaccine doseHerpes virusImmune responseSymptom improvementSignificant elevationImpact of COVID-19 vaccination
2024
A Lymph Node Immune Score (LNIS) Identifies Prognostic Immune Phenotypes Shared across Head and Neck Cancers
Karpinets T, Garden A, Rosenthal D, Fuller C, Frank S, Gunn G, Phan J, Morrison W, Lee A, Moreno A, Song X, Mitani Y, Ferrarotto R, Gross N, Zhang J, Myers J, El-Naggar A, Spiotto M. A Lymph Node Immune Score (LNIS) Identifies Prognostic Immune Phenotypes Shared across Head and Neck Cancers. International Journal Of Radiation Oncology • Biology • Physics 2024, 120: s222-s223. DOI: 10.1016/j.ijrobp.2024.07.2308.Peer-Reviewed Original ResearchHead and neck squamous cell cancerNon-small cell lung cancerLymph node metastasisPrognostic gene signatureRelapse free survivalExtranodal extensionFree survivalGene signatureImmune microenvironmentImmune scoreLymph nodesImmune phenotypeRejection subtypeHPV-positive HNSCCImmune rejectionAbsence of extranodal extensionNon-small cell lung cancer cohortsHPV-negative HNSCC patientsUnivariate Cox proportional hazards modelHead and neck cancerImmunology-related genesMetastatic lymph nodesLymph node microenvironmentSquamous cell cancerCell lung cancerARID1A suppresses R-loop-mediated STING-type I interferon pathway activation of anti-tumor immunity
Maxwell M, Hom-Tedla M, Yi J, Li S, Rivera S, Yu J, Burns M, McRae H, Stevenson B, Coakley K, Ho J, Gastelum K, Bell J, Jones A, Eskander R, Dykhuizen E, Shadel G, Kaech S, Hargreaves D. ARID1A suppresses R-loop-mediated STING-type I interferon pathway activation of anti-tumor immunity. Cell 2024, 187: 3390-3408.e19. PMID: 38754421, PMCID: PMC11193641, DOI: 10.1016/j.cell.2024.04.025.Peer-Reviewed Original ResearchImmune checkpoint blockadeAnti-tumor immunityIncreased CD8+ T cell infiltrationCD8+ T cell infiltrationT cell infiltrationType I IFN signalingGene expression signaturesICB treatmentCheckpoint blockadeIndependent of microsatellite instabilityARID1A mutationsCytolytic activityImmune phenotypeMurine modelCell infiltrationARID1A lossClinical trialsMutant cancersARID1AHuman cancersExpression signaturesGene upregulationMicrosatellite instabilityCancerInterferon
2023
Immunodeficiency with susceptibility to lymphoma with complex genotype affecting energy metabolism (FBP1, ACAD9) and vesicle trafficking (RAB27A)
Brauer N, Maruta Y, Lisci M, Strege K, Oschlies I, Nakamura H, Böhm S, Lehmberg K, Brandhoff L, Ehl S, Parvaneh N, Klapper W, Fukuda M, Griffiths G, Hennies H, Niehues T, Ammann S. Immunodeficiency with susceptibility to lymphoma with complex genotype affecting energy metabolism (FBP1, ACAD9) and vesicle trafficking (RAB27A). Frontiers In Immunology 2023, 14: 1151166. PMID: 37388727, PMCID: PMC10303925, DOI: 10.3389/fimmu.2023.1151166.Peer-Reviewed Original ResearchConceptsInborn errors of immunityHemophagocytic lymphohistiocytosisWhole-exome sequencingImmune phenotypeImpairment of NK cellsHistory of Hodgkin lymphomaExome sequencingGriscelli syndrome type 2Increased susceptibility to infectionCD8 T cellsSusceptibility to lymphomaImpaired immune regulationErrors of immunityT cell degranulationSusceptibility to infectionHodgkin lymphomaNK cellsLytic granule polarizationT cellsImmune regulationCritical treatment decisionsGranule polarizationVariable impairmentVesicle traffickingHomozygous variantSex and prior exposure jointly shape innate immune responses to a live herpesvirus vaccine
Cheung F, Apps R, Dropulic L, Kotliarov Y, Chen J, Jordan T, Langweiler M, Candia J, Biancotto A, Han K, Rachmaninoff N, Pietz H, Wang K, Tsang J, Cohen J. Sex and prior exposure jointly shape innate immune responses to a live herpesvirus vaccine. ELife 2023, 12: e80652. PMID: 36648132, PMCID: PMC9844983, DOI: 10.7554/elife.80652.Peer-Reviewed Original ResearchConceptsEarly innate responseVaccine recipientsPrior exposureInnate responseType I interferon signatureInfectious diseasesSeronegative vaccine recipientsType I IFN responseEarly antiviral responseNational InstituteInnate immune responseSystems immunology approachI IFN responseAdaptive immune phenotypesIntramural Research ProgramInterferon signatureAntibody titersVaccine trialsImmune phenotypeVirus vaccineNaive womenImmune responseSanofi PasteurDay 1Herpesvirus vaccine
2022
Increased Macrophage-Specific Arterial Infiltration Relates to Noncalcified Plaque and Systemic Immune Activation in People With Human Immunodeficiency Virus
Toribio M, Wilks M, Hedgire S, Lu M, Cetlin M, Wang M, Alhallak I, Durbin C, White K, Wallis Z, Schnittman S, Stanley T, El-Fakhri G, Lee H, Autissier P, Zanni M, Williams K, Grinspoon S. Increased Macrophage-Specific Arterial Infiltration Relates to Noncalcified Plaque and Systemic Immune Activation in People With Human Immunodeficiency Virus. The Journal Of Infectious Diseases 2022, 226: 1823-1833. PMID: 35856671, PMCID: PMC10205602, DOI: 10.1093/infdis/jiac301.Peer-Reviewed Original ResearchConceptsHuman immunodeficiency virusAtherosclerotic cardiovascular diseaseAortic plaque volumeSystemic immune activationArterial infiltrationImmune activationImmunodeficiency virusPlaque volumeHistory of clinical ASCVDCD4+/CD8+ T-cell ratioHuman immunodeficiency virus statusCD8+ T cellsMarkers of immune activationClinical atherosclerotic cardiovascular diseasePersistent immune activationT cell ratioAtherosclerotic cardiovascular disease riskT cellsImmune phenotypeNoncalcified plaqueSystemic markersASCVD riskPWHCardiovascular diseaseUptake volumeInteraction between maternal killer immunoglobulin-like receptors and offspring HLAs and susceptibility of childhood ALL
Feng Q, Zhou M, Li S, Morimoto L, Hansen H, Myint SS, Wang R, Metayer C, Kang A, Fear AL, Pappas D, Erlich H, Hollenbach JA, Mancuso N, Trachtenberg E, de Smith AJ, Ma X, Wiemels JL. Interaction between maternal killer immunoglobulin-like receptors and offspring HLAs and susceptibility of childhood ALL. Blood Advances 2022, 6: 3756-3766. PMID: 35500222, PMCID: PMC9631572, DOI: 10.1182/bloodadvances.2021006821.Peer-Reviewed Original ResearchConceptsKiller immunoglobulin-like receptorsMaternal killer immunoglobulin-like receptorsAcute lymphoblastic leukemiaChild-mother pairsImmunoglobulin-like receptorsArginase IIKIR interactionsLower riskNon-Latino white subjectsLower tumor necrosisCase-control studyEtiology of childhoodDevelopment of childhoodHLA-KIRNeonatal cytokinesCytokine levelsCytokine profileLymphoblastic leukemiaImmune factorsImmune phenotypeTumor necrosisHigh riskChildhood leukemiaCytokine controlSignificant association
2021
Diverse immune response of DNA damage repair-deficient tumors
Qing T, Jun T, Lindblad KE, Lujambio A, Marczyk M, Pusztai L, Huang KL. Diverse immune response of DNA damage repair-deficient tumors. Cell Reports Medicine 2021, 2: 100276. PMID: 34095878, PMCID: PMC8149377, DOI: 10.1016/j.xcrm.2021.100276.Peer-Reviewed Original ResearchConceptsCancer typesDDR-deficient tumorsImmune checkpoint inhibitorsHigh neoantigen loadDifferent immune phenotypesDiverse immune responsesAdaptive immune markersRepair-deficient tumorsDDR deficiencyCheckpoint inhibitorsImmunotherapy outcomesDNA damage repair deficiencyImmune infiltratesImmune markersNeoantigen loadSurvival outcomesImmune phenotypeTumor neoantigensImmune responseAnimal modelsGenomic biomarkersGermline mutationsPathway mutationsTumorsRepair deficiencyCheckpoint Inhibitor Colitis Shows Drug-Specific Differences in Immune Cell Reaction That Overlap With Inflammatory Bowel Disease and Predict Response to Colitis Therapy
Lo YC, Price C, Blenman K, Patil P, Zhang X, Robert ME. Checkpoint Inhibitor Colitis Shows Drug-Specific Differences in Immune Cell Reaction That Overlap With Inflammatory Bowel Disease and Predict Response to Colitis Therapy. American Journal Of Clinical Pathology 2021, 156: 214-228. PMID: 33555016, DOI: 10.1093/ajcp/aqaa217.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseaseCD8/FOXP3 ratioBiopsy specimensCPI patientsPD-1CD68 scoreFOXP3 ratioBowel diseasePD-L1Antibody-treated patientsCheckpoint inhibitor colitisPD-L1 groupInitial biopsy specimensPD-L1 expressionImmune cell reactionsColonic biopsy specimensDrug-specific differencesIBD groupCheckpoint inhibitorsChronicity scoreActivity scoreImmune phenotypeTherapeutic responseColitisShared pathophysiologyAbsolute quantification of tumor-infiltrating immune cells in high-grade glioma identifies prognostic and radiomics values
Kim A, Choi K, Kim M, Kim K, Kang H, Kim S, Chowdhury T, Yu H, Lee C, Lee J, Lee S, Won J, Kim J, Kim Y, Kim T, Park S, Choi S, Shin E, Park C. Absolute quantification of tumor-infiltrating immune cells in high-grade glioma identifies prognostic and radiomics values. Cancer Immunology, Immunotherapy 2021, 70: 1995-2008. PMID: 33416947, PMCID: PMC10991432, DOI: 10.1007/s00262-020-02836-w.Peer-Reviewed Original ResearchConceptsTumor-infiltrating immune cellsHigh-grade gliomasImmune cellsTumor-associated macrophagesImmune microenvironmentRadiomics signatureClinical prognostic relevanceImmune cell numbersImmune cell subpopulationsImmune microenvironment characteristicsTumor immune microenvironmentCore tissueApparent diffusion coefficient (ADC) mapsDiffusion coefficient mapsOverall survivalPrognostic impactPatient groupPrognostic relevanceClinical prognosisImmune characteristicsImmune phenotypeMedian numberM2 TAMsTumor tissueMethodsThe number
2019
Molecular Pathway Analysis Indicates a Distinct Metabolic Phenotype in Women With Right-Sided Colon Cancer
Sun Y, Mironova V, Chen Y, Lundh EPF, Zhang Q, Cai Y, Vasiliou V, Zhang Y, Garcia-Milian R, Khan SA, Johnson CH. Molecular Pathway Analysis Indicates a Distinct Metabolic Phenotype in Women With Right-Sided Colon Cancer. Translational Oncology 2019, 13: 42-56. PMID: 31760268, PMCID: PMC6883319, DOI: 10.1016/j.tranon.2019.09.004.Peer-Reviewed Original ResearchRight-sided colon cancerLeft-sided colon cancerColon cancerAnatomical locationTumor tissueAnti-tumor immune responseGene Expression OmnibusImportant predictive markerPoor clinical outcomeTumor anatomical locationClinical outcomesPredictive markerPrimary tumorImmune phenotypeDistinct metabolic phenotypesImmune responseLower incidenceTreatment responseSex-specific differencesMolecular pathway analysisClinical importanceCancerProtein kinase alpha subunitBiotechnology Information Gene Expression OmnibusWomen
2016
Cellular Immunophenotyping: Industrial Technologies and Emerging Tools
Brower K, Fan R. Cellular Immunophenotyping: Industrial Technologies and Emerging Tools. 2016, 57-74. DOI: 10.1002/9783527801312.ch3.Peer-Reviewed Original ResearchCellular immune phenotypeHeterogeneous immune cellsImmune cell phenotypingPatient's immune statusDifferent patient cohortsImmune effector functionsDrug efficacy testingCellular immunityImmune statusPatient cohortImmune cellsImmune phenotypePatient responseEffector functionsDisease prognosisClinical settingCell phenotypingEfficacy testingGold standardCell populationsEffector moleculesImmunitySurface marker detectionPrognosisCohortPre-BCR signaling in precursor B-cell acute lymphoblastic leukemia regulates PI3K/AKT, FOXO1 and MYC, and can be targeted by SYK inhibition
Köhrer S, Havranek O, Seyfried F, Hurtz C, Coffey G, Kim E, ten Hacken E, Jäger U, Vanura K, O'Brien S, Thomas D, Kantarjian H, Ghosh D, Wang Z, Zhang M, Ma W, Jumaa H, Debatin K, Müschen M, Meyer L, Davis R, Burger J. Pre-BCR signaling in precursor B-cell acute lymphoblastic leukemia regulates PI3K/AKT, FOXO1 and MYC, and can be targeted by SYK inhibition. Leukemia 2016, 30: 1246-1254. PMID: 26847027, PMCID: PMC5459356, DOI: 10.1038/leu.2016.9.Peer-Reviewed Original ResearchConceptsB-cell acute lymphoblastic leukemiaSpleen tyrosine kinaseAcute lymphoblastic leukemiaPI3K/AktLymphoblastic leukemiaTherapeutic targetPrecursor B-cell acute lymphoblastic leukemiaPromising new therapeutic targetNew therapeutic targetsGene expression signaturesImmune phenotypeImportant downstream mediatorSYK inhibitionMouse modelPre-BCR signalingReceptor signalingDownstream mediatorExpression signaturesGenetic disruptionLeukemiaExquisite dependencyTyrosine kinaseAktFOXO1Signaling
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