2025
Lung adenocarcinoma-derived IFN-γ promotes growth by modulating CD8+ T cell production of CCR5 chemokines
Kratzmeier C, Taheri M, Mei Z, Lim I, Khalil M, Carter-Cooper B, Fanaroff R, Ong C, Schneider E, Chang S, Leyder E, Li D, Luzina I, Banerjee A, Krupnick A. Lung adenocarcinoma-derived IFN-γ promotes growth by modulating CD8+ T cell production of CCR5 chemokines. Journal Of Clinical Investigation 2025 PMID: 40553564, DOI: 10.1172/jci191070.Peer-Reviewed Original ResearchCD8+ T cellsIFN-gCCR5 chemokinesT cellsCD4+Foxp3+ T regulatory cellsCD8+ T-cell productionCancer cellsHuman lung cancer patientsLevels of IFN-gT regulatory cellsMurine lung adenocarcinomaLung adenocarcinoma modelLung cancer patientsMechanisms of immunoregulationCell line modelsLung cancer cellsTumor bedAdenocarcinoma modelTh1 cytokinesTumor microenvironmentImmunological environmentImmunoregulatory pathwaysCarcinogen-inducedTumor growthLung cancerPOS0015 Zasocitinib (TAK-279) exhibits high levels of TYK2 inhibition and no inhibition of JAK 1/3 when compared with licensed TYK2 and JAK inhibitors
Mehrotra S, Sano Y, Wilson E, Durairaj C, Kong K, Xia G, Dunbar F, Halkowycz P, Spector T, Bunick C, McInnes I. POS0015 Zasocitinib (TAK-279) exhibits high levels of TYK2 inhibition and no inhibition of JAK 1/3 when compared with licensed TYK2 and JAK inhibitors. Annals Of The Rheumatic Diseases 2025, 84: 333. DOI: 10.1016/j.ard.2025.05.412.Peer-Reviewed Original ResearchBaricitinib 4 mgJanus kinase inhibitorsTyrosine kinase 2Plasma concentrationsTreatment of immune-mediated inflammatory diseasesJanus kinaseImmune-mediated inflammatory diseasesInhibition of tyrosine kinase 2Published population pharmacokinetic modelTyk2-mediated signalingTyrosine kinase 2 inhibitionLate-stage clinical developmentPopulation pharmacokinetic modelTyrosine kinase 2 inhibitorWhole blood culturesDrug plasma concentrationsTYK2 inhibitionInhibition of Janus kinaseIL-12/18Approved doseClinical doseIFN-gDeucravacitinibHealthy volunteersIL-2Targeting Neuronal Nitric Oxide Synthase (nNOS) as a Novel Approach to Enhancing the Anti-Melanoma Activity of Immune Checkpoint Inhibitors
Patel A, Tong S, Lozada K, Awasthi A, Silverman R, Totonchy J, Yang S. Targeting Neuronal Nitric Oxide Synthase (nNOS) as a Novel Approach to Enhancing the Anti-Melanoma Activity of Immune Checkpoint Inhibitors. Pharmaceutics 2025, 17: 691. PMID: 40574005, PMCID: PMC12196278, DOI: 10.3390/pharmaceutics17060691.Peer-Reviewed Original ResearchPeripheral blood mononuclear cellsNeuronal nitric oxide synthaseNeuronal nitric oxide synthase inhibitorActivity of immune checkpoint inhibitorsT cell activationImmune checkpoint inhibitorsAnti-melanoma activityT cellsTargeting nNOSNitric oxide synthaseCheckpoint inhibitorsIFN-gCD8<sup>+</sup>PD-1<sup>+</sup> T cellsInterleukin-2PD-1<sup>+</sup> T cellsEffects of nNOS inhibitionIL-2-secreting T cellsImmune responseMouse peripheral blood mononuclear cellsOxide synthaseAnti-PD-1Immune checkpoint blockadeMelanoma immune responsePD-1 blockadePD-L1 expressionCD1d‐iNKT Axis in Infectious Diseases: Lessons Learned From the Past
Chatterjee P, Brahma S, Cresswell P, Bandyopadhyay S. CD1d‐iNKT Axis in Infectious Diseases: Lessons Learned From the Past. Scandinavian Journal Of Immunology 2025, 101: e70024. PMID: 40243400, DOI: 10.1111/sji.70024.Peer-Reviewed Original ResearchConceptsINKT cellsLipid antigensDiverse array of cytokinesRecognition of lipid antigensEra of immunotherapyINKT cell responsesInnate-like propertiesAntigen-presenting moleculesArray of cytokinesInfectious diseasesImmunotherapeutic strategiesBridge innateT lymphocytesAdjunctive therapyIFN-gIL-13IL-4Antimicrobial treatmentArray of lipidsInfluence immune reactionsAdaptive immunityImmune responseCases of infectious diseasesImmune reactionsGlycolipid antigensA Phase I, First-in-Human, Dose-Escalation, Expansion Trial of Cytokine-Encoding Synthetic mRNA Mixture Alone or with Cemiplimab in Advanced Solid Tumors
Bechter O, Loquai C, Champiat S, Baurain J, Grob J, Utikal J, Rottey S, Berrocal A, Hassel J, Arance A, Sanmamed M, Boers-Sonderen M, Gastman B, Gebhardt C, Delafontaine B, Sahin U, Türeci Ö, Brueck P, Abbadessa G, Marpadga R, Lee H, Yang Y, Buday B, Di Genova G, Wang H, Xia B, Lee J, Lebbe C. A Phase I, First-in-Human, Dose-Escalation, Expansion Trial of Cytokine-Encoding Synthetic mRNA Mixture Alone or with Cemiplimab in Advanced Solid Tumors. Clinical Cancer Research 2025, 31: 2358-2369. PMID: 40152791, PMCID: PMC12163594, DOI: 10.1158/1078-0432.ccr-24-1983.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCytokinesFemaleGranulocyte-Macrophage Colony-Stimulating FactorHumansInterferon alpha-2Interleukin-12Interleukin-15MaleMaximum Tolerated DoseMiddle AgedNeoplasmsRNA, MessengerTreatment OutcomeConceptsAdvanced solid tumorsMaximum administered doseSolid tumorsCombination therapyEscalation phaseTreated with anti-PD-1 therapyTreated with anticancer therapyAnti-PD-1 therapyTreatment-related adverse eventsDose level 8Predefined dose levelsInjection-site painFirst-in-humanPlasma cytokine concentrationsDose escalationAntitumor responsePartial responseIntratumoral administrationExpansion trialIL-15IFN-gCemiplimabAdverse eventsCytokine concentrationsDose levelsEpigenetic therapy sensitizes anti–PD-1 refractory head and neck cancers to immunotherapy rechallenge
Qin T, Mattox A, Campbell J, Park J, Shin K, Li S, Sadow P, Faquin W, Micevic G, Daniels A, Haddad R, Garris C, Pittet M, Mempel T, ONeill A, Sartor M, Pai S. Epigenetic therapy sensitizes anti–PD-1 refractory head and neck cancers to immunotherapy rechallenge. Journal Of Clinical Investigation 2025, 135: e181671. PMID: 40091844, PMCID: PMC11910227, DOI: 10.1172/jci181671.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsAzacitidineB7-H1 AntigenEpigenesis, GeneticFemaleHead and Neck NeoplasmsHumansImmune Checkpoint InhibitorsImmunotherapyMaleMiddle AgedProgrammed Cell Death 1 ReceptorSquamous Cell Carcinoma of Head and NeckTumor MicroenvironmentConceptsHead and neck squamous cell carcinomaTumor microenvironmentProlonged OSOverall survivalIFN-gCD8+ T cell infiltrationCD4+ T regulatory cellsOn-treatment tumor biopsiesNeck squamous cell carcinomaSystemic host immune responseBackgroundImmune checkpoint blockadeMetastatic (R/MMedian overall survivalPD-L1 expressionT cell infiltrationLocal tumor microenvironmentT regulatory cellsSquamous cell carcinomaBiologically effective dosePhase 1b clinical trialHost immune responseCheckpoint blockadeOS ratesPD-L1Tumor biopsiesDecreased T helper 1 cell function underlies recurrent sinopulmonary infections in the 17q12 deletion syndrome
Shin J, Shin H, Gutierrez A, Yoo N, Par-Young J, Osmani L, Shin M, Sanchez-Lara P, Bucala R, Soffer G, Kang I. Decreased T helper 1 cell function underlies recurrent sinopulmonary infections in the 17q12 deletion syndrome. EBioMedicine 2025, 112: 105578. PMID: 39891996, PMCID: PMC11840234, DOI: 10.1016/j.ebiom.2025.105578.Peer-Reviewed Original ResearchConceptsCD4<sup>+</sup> T cellsRecurrent sinopulmonary infectionsT cell functionRNA-seq analysisT cellsHealthy controlsSinopulmonary infectionsRNA-seqT-betIFN-gFrequency of CD4<sup>+</sup> T cellsCD4<sup>+</sup> T cell functionTh1 transcription factor T-betDeletion syndromeFlow cytometryCompared to age-matched healthy controlsTranscription factor T-betDecreased T-betUrinary tract abnormalitiesAge-matched healthy controlsMultiplex assayDownstream effector cytokinesEffector cytokinesRecurrent infectionsTh17 cytokinesCrosstalk Between nNOS/NO and COX-2 Enhances Interferon-Gamma-Stimulated Melanoma Progression
Patel A, Tong S, Roosan M, Syed B, Awasthi A, Silverman R, Yang S. Crosstalk Between nNOS/NO and COX-2 Enhances Interferon-Gamma-Stimulated Melanoma Progression. Cancers 2025, 17: 477. PMID: 39941844, PMCID: PMC11816268, DOI: 10.3390/cancers17030477.Peer-Reviewed Original ResearchNeuronal nitric oxide synthaseIFN-gPro-tumorigenic activityCOX-2Human melanoma xenograft mouse modelMelanoma progressionMelanoma cellsFlow cytometryInduction of neuronal nitric oxide synthaseNeuronal nitric oxide synthase blockadeIn vivo antitumor efficacyMelanoma xenograft mouse modelMelanoma tumor microenvironmentLevels of PGE<sub>2</sub>PD-L1 expressionAnticancer immune responseMelanoma tumor growth in vivoCOX-2 expression levelsAnalysis of patientsInduction of COX-2Increased intracellular NO levelsSTAT3 inhibitor NapabucasinNitric oxideInhibited COX-2 expressionXenograft mouse model
2024
R-Spondin 1 Suppresses Inflammatory Cytokine Production in Human Cortical Astrocytes
Logan R, Bhatta S, Sutova H, Hafler B, Miller S. R-Spondin 1 Suppresses Inflammatory Cytokine Production in Human Cortical Astrocytes. Neuroglia 2024, 5: 445-451. DOI: 10.3390/neuroglia5040028.Peer-Reviewed Original ResearchCentral nervous systemCytokine releaseSignaling pathwayCentral nervous system inflammationR-spondinStem cell-derived astrocytesInfluence central nervous systemHuman induced pluripotent stem cell-derived astrocytesCytokine array kitSuppression of inflammatory cytokinesModulate cytokine releaseWnt signalingInfluence inflammatory responsesModulate immune responsesInflammatory cytokine productionCytokine-cytokine receptor interactionInflammatory cytokine releaseContext of inflammationLGR6 receptorsPathway enrichment analysisCXCL12 levelsHuman cortical astrocytesIL-23TNF signaling pathwayIFN-gPlasma NGAL, not IFN-γ, predicts early treatment response in drug-naïve Chinese Han schizophrenia patients
Sun X, Li M, Qiu Y, Su Q, Wang J, Bi F, Li J. Plasma NGAL, not IFN-γ, predicts early treatment response in drug-naïve Chinese Han schizophrenia patients. Schizophrenia Research 2024, 274: 457-463. PMID: 39515255, DOI: 10.1016/j.schres.2024.10.025.Peer-Reviewed Original ResearchDrug-naive schizophrenia patientsSchizophrenia patientsNeutrophil gelatinase-associated lipocalinNeutrophil gelatinase-associated lipocalin concentrationsEarly treatment responseDuration of untreated illnessTreatment responseIFN-gHealthy controlsNGAL concentrationsEarly prediction of treatment efficacyPlasma neutrophil gelatinase-associated lipocalinNeutrophil gelatinase-associated lipocalin levelsUntreated illnessPrediction of treatment efficacyPredicting early treatment responsePlasma NGAL concentrationsWeeks of treatmentIFN-g levelsPersonalized treatment strategiesLogistic regression analysisBaseline NGAL concentrationLongitudinal studySchizophreniaTreatment outcomesSelenomethionine supplementation mitigates fluoride-induced liver apoptosis and inflammatory reactions by blocking Parkin-mediated mitophagy in mice
Wang T, Li H, Li Y, Li M, Zhao H, Zhang W, Zhao T, Wang Y, Wang J, Wang J. Selenomethionine supplementation mitigates fluoride-induced liver apoptosis and inflammatory reactions by blocking Parkin-mediated mitophagy in mice. The Science Of The Total Environment 2024, 951: 175458. PMID: 39142410, DOI: 10.1016/j.scitotenv.2024.175458.Peer-Reviewed Original ResearchParkin-mediated mitophagyCysteinyl aspartate specific proteinase 3Protein expression levelsLight chain 3Expression levelsInterleukin-6Wild-typeLiver damageContents of proinflammatory factorsTumor necrosis factor-aNuclear factor kappa BLevels of liver functionMitochondrial fusionFactor kappa BParkin-/-Inflammatory signaling pathwaysMicrotubule-associated protein light chain 3MitophagyInterferon-gMitochondrial alterationsProtein light chain 3Gene knockoutIFN-gFluorosis miceLiver functionDevelopment of anex vivo patient-derived tumor model (PDTM) to assess the tumor microenvironment in renal cell carcinoma (RCC)
Kashima S, Gupta R, Moritz V, Sadak K, Adeniran A, Humphrey P, Dinulescu D, Palmer D, Hammond S, Bosenberg M, Hurwitz M, Kenney P, Braun D. Development of anex vivo patient-derived tumor model (PDTM) to assess the tumor microenvironment in renal cell carcinoma (RCC). The Oncologist 2024, 29: s5-s6. PMCID: PMC11301923, DOI: 10.1093/oncolo/oyae181.008.Peer-Reviewed Original ResearchRCC tumor microenvironmentPatient-derived tumor modelsRenal cell carcinomaImmune checkpoint inhibitorsT cell functionPeripheral blood mononuclear cellsEnzyme-linked immunosorbent assayTumor microenvironmentT cellsFlow cytometryTumor fragmentsIFN-gTumor modelTumor samplesCytokine productionHealthy donor peripheral blood mononuclear cellsImpact of immune checkpoint inhibitorsAnti-PD-1 monoclonal antibodyDonor peripheral blood mononuclear cellsCD4+CD25+ regulatory T cellsCD8+ T cell populationsResection of renal cell carcinomaSurgical resection of renal cell carcinomaAnti-PD-1 antibodyMetastatic renal cell carcinomaGranuloma Annulare Exhibits Mixed Immune and Macrophage Polarization Profiles with Spatial Transcriptomics
Mohanty C, Singh C, Daccache J, Damsky W, Kendziorski C, Yan D, Prasad A, Zhang D, Keenan T, Drolet B, Ahmad N, Shields B. Granuloma Annulare Exhibits Mixed Immune and Macrophage Polarization Profiles with Spatial Transcriptomics. Journal Of Investigative Dermatology 2024, 145: 109-121. PMID: 38844128, DOI: 10.1016/j.jid.2024.04.024.Peer-Reviewed Original ResearchGranuloma annulareGranulomatous inflammationFDA-approved therapiesInflammatory signaling cascadesImpact of GAIFN-gImmune cellsInterleukin-32Idiopathic conditionTh2 signalsAdaptive immunityInterstitial patternMacrophage activationGene expression changesMolecular driversQuality of lifeGenome-wide gene expression changesMacrophage polarizationGranulomaMacrophagesTissue remodelingInflammationTNF signalingLocal gene expression patternsSpatial transcriptomicsHLA class-I antigen presentation machinery (APM) alterations mediate immune evasion in lung cancer brain metastases.
Vilariño N, Lopez De Rodas M, Ranjan K, Costantini A, Villalba M, Lu B, Kravitz C, Nadal E, Goldberg S, Nguyen D, Schalper K. HLA class-I antigen presentation machinery (APM) alterations mediate immune evasion in lung cancer brain metastases. Journal Of Clinical Oncology 2024, 42: e14014-e14014. DOI: 10.1200/jco.2024.42.16_suppl.e14014.Peer-Reviewed Original ResearchLung cancer brain metastasisPrimary lung tumorsTumor-infiltrating lymphocytesImmune checkpoint inhibitorsCancer brain metastasesAntigen presentation machineryB2M expressionIFN-gBrain metastasesB2MImmune evasionAssociated with shorter overall survivalMultiplexed quantitative immunofluorescenceM expressionExpression of B2MB2M levelsExpression of pSTAT1Shorter overall survivalUnfavorable clinical featuresNo significant associationAssociated with unfavorable clinical featuresCheckpoint inhibitorsImmunotherapy resistanceProperties of tumorsPresentation machinerySLAMF7+ CD8+ T cells exhibit decreased anti-tumor responses in renal cell carcinoma
Wirth L, Hugaboom M, Street K, Ruthen N, Jegede O, Schindler N, McDermott D, Plimack E, Sosman J, Haas N, Hurwitz M, Hammers H, Signoretti S, Atkins M, Wu C, Braun D. SLAMF7+ CD8+ T cells exhibit decreased anti-tumor responses in renal cell carcinoma. The Journal Of Immunology 2024, 212: 1491_5876-1491_5876. DOI: 10.4049/jimmunol.212.supp.1491.5876.Peer-Reviewed Original ResearchCD8+ T cellsImmune-checkpoint inhibitorsRenal cell carcinomaCD8+ T-cell effector functionT cell effector functionT cellsCell carcinomaResistance to immune-checkpoint inhibitorsEffector functionsPopulation of CD8+ T cellsCD3+ T cellsTreatment of renal cell carcinomaHealthy human PBMCTumor-infiltrating lymphocytesAnti-tumor responsesPatient T cellsReduction of pro-inflammatory cytokinesAnti-tumor functionPro-inflammatory cytokinesSingle-cell transcriptome analysisNivolumab monotherapySLAMF7 expressionClinical benefitGranzyme BIFN-gDevelopment and comparison of immunologic assays to detect primary RSV infections in infants
Anderson L, Jadhao S, Hussaini L, Ha B, McCracken C, Gibson T, Yildirim I, Yi J, Stephens K, Korski C, Kao C, Sun H, Lee C, Jaunarajs A, Rostad C, Anderson E. Development and comparison of immunologic assays to detect primary RSV infections in infants. Frontiers In Immunology 2024, 14: 1332772. PMID: 38283339, PMCID: PMC10811012, DOI: 10.3389/fimmu.2023.1332772.Peer-Reviewed Original ResearchConceptsRespiratory syncytial virusIgG enzyme immunoassayNeutralizing antibody assaysELISPOT assayAntibody assayRSV antibodiesEnzyme immunoassayRSV infectionSubgroup ARespiratory syncytial virus seasonDocumented RSV infectionPrimary RSV infectionEffective respiratory syncytial virusVaccine clinical trialsEvidence of past infectionEpidemiological studiesRed cell lysisYoung childrenMaternal microchimerismPBMC specimensPregnant womenIFN-gSyncytial virusAntibody enzyme immunoassayELISPOT
2023
Th1 bias of liver mucosal‐associated invariant T cells promotes hepatic gluconeogenesis in type 2 diabetes mellitus
Tang W, Ge K, Shen L, Wang H, Feng W, Sun X, Chu X, Zhu D, Yin H, Bi Y. Th1 bias of liver mucosal‐associated invariant T cells promotes hepatic gluconeogenesis in type 2 diabetes mellitus. Diabetes/Metabolism Research And Reviews 2023, 39: e3620. PMID: 36738300, DOI: 10.1002/dmrr.3620.Peer-Reviewed Original ResearchConceptsHepatic MAIT cellsMAIT cellsMAIT cell subsetsType 2 diabetes mellitusInnate-like T cell subsetMucosal-associated invariant T (MAIT) cellsHepatic gluconeogenesisMucosal-associated invariant T cellsExpression of pyruvate carboxylaseGene expression of pyruvate carboxylaseCell subsetsExpression of genesT2DM subjectsInvariant T cellsIFN-gMAIT cell frequencyPyruvate carboxylaseProduction of interleukin-17HepG2 cells co-culturedT cell subsetsTumor necrosis factor-aDevelopment of type 2 diabetes mellitusGene expressionDiagnosed T2DM subjectsMetabolic homoeostasis
2021
Intravital imaging of interactions between iNKT and kupffer cells to clear free lipids during steatohepatitis
Wang H, Li L, Li Y, Li Y, Sha Y, Wen S, You Q, Liu L, Shi M, Zhou H. Intravital imaging of interactions between iNKT and kupffer cells to clear free lipids during steatohepatitis. Theranostics 2021, 11: 2149-2169. PMID: 33500717, PMCID: PMC7797696, DOI: 10.7150/thno.51369.Peer-Reviewed Original ResearchConceptsInvariant natural killer TInvariant natural killer T cellsINKT cellsAdoptive transfer of iNKT cellsGenes related to phagocytosisKupffer cellsMethionine-choline-deficientNatural killer TPopulation of innate immune cellsConfocal live imagingTranscriptome sequencingCell clustersInnate immune cellsIFN-g expressionLiver fibrosis developmentKiller TStages of steatohepatitisPotential therapeutic strategyLipid processingDiet-induced steatohepatitisAdoptive transferLiver steatohepatitisIFN-gImmune cellsLipid phagocytosis
2020
CTIM-28. PHASE 2 TRIAL OF CONTROLLED IL-12 IN COMBINATION WITH PD-1 INHIBITOR IN ADULT SUBJECTS WITH RECURRENT GLIOBLASTOMA (rGBM)
Lukas R, Chiocca E, Bush N, Landolfi J, Cavaliere R, Yu J, Kurz S, Demars N, Buck J, Hadar N, Miao J, Loewy J, Wang Y, Gelb A, Cooper L. CTIM-28. PHASE 2 TRIAL OF CONTROLLED IL-12 IN COMBINATION WITH PD-1 INHIBITOR IN ADULT SUBJECTS WITH RECURRENT GLIOBLASTOMA (rGBM). Neuro-Oncology 2020, 22: ii39-ii39. PMCID: PMC7650356, DOI: 10.1093/neuonc/noaa215.162.Peer-Reviewed Original ResearchPD-1 inhibitorsImmune-mediated anti-tumor effectsAnti-tumor effectsRecurrent glioblastomaIL-12PD-1Overall survivalFollow-upIncreased PD-1 expressionIL-12 therapyPD-1 expressionPhase 2 trialPhase 1 trialPost-treatment biopsiesGene therapy candidateSurvival dataEndogenous cytokine productionIFN-g levelsTumor cell heterogeneityFunctional IL-12Blood-brain barrierCombination immunotherapyIT injectionSafety profileIFN-gMacrophage inhibitory factor (MIF) gene polymorphisms are associated with disease susceptibility and with circulating MIF levels in active non‐segmental vitiligo in patients from western Mexico
Garcia‐Orozco A, Martinez‐Magaña I, Riera‐Leal A, Muñoz‐Valle J, Martinez‐Guzman M, Quiñones‐Venegas R, Sánchez‐Zuno G, Fafutis‐Morris M. Macrophage inhibitory factor (MIF) gene polymorphisms are associated with disease susceptibility and with circulating MIF levels in active non‐segmental vitiligo in patients from western Mexico. Molecular Genetics & Genomic Medicine 2020, 8: e1416. PMID: 32705792, PMCID: PMC7549602, DOI: 10.1002/mgg3.1416.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibition factorNon-segmental vitiligoActive non-segmental vitiligoSerum concentrationsActivation of immune cellsExpression of MIFCirculating MIF levelsMacrophage inhibitory factorWestern Mexican populationPathogenesis of vitiligoAssociated with disease susceptibilityMigration inhibition factorIn situ expressionMIF levelsActive vitiligoAutomated immunohistochemistryDisease activityIFN-gReal-time PCRGene polymorphismsImmune cellsControl subjectsProinflammatory cytokinesTNF-aIL-1B
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply