2025
Autonomic modulation of the immune response and implications for CNS malignancies
Wachsmuth L, Srinivasan E, Puviindran B, Haskell-Mendoza A, DeSpenza T, Fecci P. Autonomic modulation of the immune response and implications for CNS malignancies. Npj Precision Oncology 2025, 9: 168. PMID: 40483275, PMCID: PMC12145445, DOI: 10.1038/s41698-025-00957-y.Peer-Reviewed Original ResearchCentral nervous systemAntitumor immune responseImmune responseAutonomic nervous systemNervous systemCentral nervous system malignanciesCentral nervous system inflammationModulation of immune responsesCentral nervous system inputImmune cell functionRegulate immune responsesIntracranial malignanciesImmune cellsMalignancyAutonomic modulationNeuro-immunologyCell functionImmune organsSignaling pathwayGlobal physiological processesTripartite interactionResponseInflammationCancerPhysiological processesTumor microenvironment of non-small cell lung cancer impairs immune cell function among people with HIV
Desai S, Salahuddin S, Yusuf R, Ranjan K, Gu J, Osmani L, Lin Y, Mehta S, Talmon R, Kang I, Kluger Y, Zhao H, Schalper K, Emu B. Tumor microenvironment of non-small cell lung cancer impairs immune cell function among people with HIV. Journal Of Clinical Investigation 2025 PMID: 40459946, DOI: 10.1172/jci177310.Peer-Reviewed Original ResearchNon-small cell lung cancerTumor microenvironmentImmune cellsLung cancerCohort of non-small cell lung cancerExpression of PD-1Impairs anti-tumor responsesTumor-infiltrating CD8+Tumor-specific immune responsesCD4+ T cellsHIV-associated tumorsInfiltrating CD8+Expression of immunoregulatory moleculesAnti-tumor responsesTumor-associated macrophagesCell lung cancerImmune cell functionNSCLC cell linesPD-1Tumor killingBlocker therapyCD8+LAG-3Immune landscapeImmunoregulatory phenotype
2024
A phase 1b study of NC410 in combination with pembrolizumab in immune checkpoint inhibitor (ICI) naïve, and refractory microsatellite stable (MSS)/microsatellite instability-low (MSI-L) colorectal cancer (CRC) and ovarian cancer.
Christenson E, Mahadevan D, Kazmi S, Manda S, Sohal D, Hutson T, Fu S, Martz A, Kordahi S, Barbu E, Flies D, Langermann S, Chisamore M, Gutierrez M, Matrana M, Spira A, Wadlow R, Guha U, Myint H, Le D. A phase 1b study of NC410 in combination with pembrolizumab in immune checkpoint inhibitor (ICI) naïve, and refractory microsatellite stable (MSS)/microsatellite instability-low (MSI-L) colorectal cancer (CRC) and ovarian cancer. Journal Of Clinical Oncology 2024, 42: 2538-2538. DOI: 10.1200/jco.2024.42.16_suppl.2538.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsImmune cell infiltrationOvarian cancerColorectal cancerICI therapyCell infiltrationAdvanced metastatic colorectal cancerPromote immune cell infiltrationResistance to ICI therapyEffector memory T cellsPeripheral blood immunophenotypingPhase 1b/2 studyDose of pembrolizumabData cut-offMetastatic colorectal cancerMetastatic solid tumorsMemory T cellsColorectal cancer subjectsImmune cell functionHuman IgG1 Fc domainAnti-tumor activityTumor extracellular matrixModified toxicity probability intervalExtracellular matrixCheckpoint inhibitors
2023
Maternal 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 loss
2022
Regulatory role of KCa3.1 in immune cell function and its emerging association with rheumatoid arthritis
Lin Y, Zhao Y, Zhang H, Hao W, Zhu R, Wang Y, Hu W, Zhou R. Regulatory role of KCa3.1 in immune cell function and its emerging association with rheumatoid arthritis. Frontiers In Immunology 2022, 13: 997621. PMID: 36275686, PMCID: PMC9580404, DOI: 10.3389/fimmu.2022.997621.Peer-Reviewed Original ResearchConceptsRheumatoid arthritisSynovial inflammationImmune cellsCollagen antibody-induced arthritis modelAntibody-induced arthritis modelCartilage/bone destructionPathogenesis of RACommon autoimmune diseaseImmune cell functionPotential therapeutic targetIntermediate-conductance CaImmune balanceRA patientsBone destructionImmune dysfunctionChronic inflammationArthritis modelAutoimmune diseasesPeripheral bloodArticular synoviumPathological progressionCartilage damageKCa3.1 channelsTherapeutic targetAbnormal activationAHCC®, a Standardized Extract of Cultured Lentinula Edodes Mycelia, Promotes the Anti-Tumor Effect of Dual Immune Checkpoint Blockade Effect in Murine Colon Cancer
Park HJ, Boo S, Park I, Shin MS, Takahashi T, Takanari J, Homma K, Kang I. AHCC®, a Standardized Extract of Cultured Lentinula Edodes Mycelia, Promotes the Anti-Tumor Effect of Dual Immune Checkpoint Blockade Effect in Murine Colon Cancer. Frontiers In Immunology 2022, 13: 875872. PMID: 35514996, PMCID: PMC9066372, DOI: 10.3389/fimmu.2022.875872.Peer-Reviewed Original ResearchConceptsDual immune checkpoint blockadeImmune checkpoint blockadeAnti-tumor effectsCheckpoint blockadeBearing miceStandardized extractTumor growthMC38 tumor-bearing miceGut microbiomePD-1/CTLATumor-infiltrating CD8Cell functionCancer bearing miceT cell functionKi-67 expressionImmune cell functionMurine colon cancerTumor bearing miceTumor-bearing miceTreatment of cancerTreatment strategiesT cellsTherapeutic effectGranzyme BColon cancer
2021
mTORC1 Signaling Regulates Proinflammatory Macrophage Function and Metabolism.
Collins S, Oh M, Sun I, Chan-Li Y, Zhao L, Powell J, Horton M. mTORC1 Signaling Regulates Proinflammatory Macrophage Function and Metabolism. The Journal Of Immunology 2021, 207: 913-922. PMID: 34290107, DOI: 10.4049/jimmunol.2100230.Peer-Reviewed Original ResearchConceptsKey regulatorImmune cell functionEnhanced histone acetylationCell functionRapid energy sourceClass III histoneDifferentiation of macrophagesHistone acetylationMacrophage functionMTORC1 signalingCellular metabolismOxidative phosphorylationCell metabolismMTOR signalingGlycolytic metabolismAntimicrobial compoundsGenetic deletionM2 macrophagesMouse macrophagesProper wound healingMetabolic programmingSignificant defectsM1 functionImmune cell metabolismSignaling
2020
Lifting the innate immune barriers to antitumor immunity
Rothlin CV, Ghosh S. Lifting the innate immune barriers to antitumor immunity. Journal For ImmunoTherapy Of Cancer 2020, 8: e000695. PMID: 32273348, PMCID: PMC7254113, DOI: 10.1136/jitc-2020-000695.BooksConceptsImmune responseImmune systemInnate immunityT-cell checkpoint inhibitorsMyeloid-derived suppressor cellsInnate immune cell functionBenefit of immunotherapyNatural killer cellsT cell activityInnate immune barrierInnate immune cellsT cell checkpointAnticancer immune responseAdaptive immune responsesImmune cell functionActivated T cellsAnticancer treatment modalitiesLarger patient poolCheckpoint inhibitorsAntitumor immunitySuppressor cellsDendritic cellsPD-L1Exaggerated inflammationKiller cells
2019
Genome-wide characterization of cytosine-specific 5-hydroxymethylation in normal breast tissue
Wilkins O, Johnson K, Houseman E, King J, Marsit C, Christensen B. Genome-wide characterization of cytosine-specific 5-hydroxymethylation in normal breast tissue. Epigenetics 2019, 15: 398-418. PMID: 31842685, PMCID: PMC7153548, DOI: 10.1080/15592294.2019.1695332.Peer-Reviewed Original ResearchConceptsGenome-wide characterizationGenome-wide patternsGenome-wide mapsGene regulatory programsActive chromatinGenomic lociGene regulationTranscriptional inactivityRegulatory regionsGene regionMammalian tissuesRegulatory programsCpG lociDNA treatmentImmune cell functionCell functionLociLactate oxidationNormal breast tissueIndependent data setsPre-invasive breast cancerRecent evidenceHeterochromatinChromatinBisulfiteNorovirus Changes Susceptibility to Type 1 Diabetes by Altering Intestinal Microbiota and Immune Cell Functions
Pearson JA, Tai N, Ekanayake-Alper DK, Peng J, Hu Y, Hager K, Compton S, Wong FS, Smith PC, Wen L. Norovirus Changes Susceptibility to Type 1 Diabetes by Altering Intestinal Microbiota and Immune Cell Functions. Frontiers In Immunology 2019, 10: 2654. PMID: 31798584, PMCID: PMC6863139, DOI: 10.3389/fimmu.2019.02654.Peer-Reviewed Original ResearchConceptsExpansion of TregsNOD miceT cellsMNV4 infectionMucosal immunityNon-obese diabetic (NOD) mouse modelGerm-free NOD miceFirmicutes/Bacteroidetes ratioProinflammatory T cellsRole of norovirusesTuft cell markersDevelopment of T1DInflammatory T cellsCommon enteric virusesB cell subsetsDiabetic mouse modelImmune cell functionType 1 diabetes susceptibilityEnteric virusesNaïve splenocytesT1D protectionTreg numbersImmunological changesMucosal antibodiesT1D developmentGlutamine blockade induces divergent metabolic programs to overcome tumor immune evasion
Leone R, Zhao L, Englert J, Sun I, Oh M, Sun I, Arwood M, Bettencourt I, Patel C, Wen J, Tam A, Blosser R, Prchalova E, Alt J, Rais R, Slusher B, Powell J. Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion. Science 2019, 366: 1013-1021. PMID: 31699883, PMCID: PMC7023461, DOI: 10.1126/science.aav2588.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAzo CompoundsCaproatesCD8-Positive T-LymphocytesCitric Acid CycleEnergy MetabolismFemaleGlucoseGlutamineImmunologic MemoryImmunotherapy, AdoptiveLymphocyte ActivationLymphocytes, Tumor-InfiltratingMaleMice, Inbred BALB CMice, Inbred C57BLNeoplasms, ExperimentalTumor EscapeTumor MicroenvironmentConceptsEffector T cellsT cellsTumor immune evasionCancer cellsPotent antitumor responsesImmune cell functionAntitumor responseImmunosuppressive microenvironmentTumor immunotherapyCancer immunotherapyMice suppressesImmune evasionCell functionOxidative metabolismGlycolytic metabolismGlutamine antagonistImmunotherapyMetabolic characteristicsMetabolic programsTumorsMetabolic checkpointDivergent changesMetabolismCellsAntagonismPhospholipids: Pulling Back the Actin Curtain for Granule Delivery to the Immune Synapse
Gawden-Bone C, Griffiths G. Phospholipids: Pulling Back the Actin Curtain for Granule Delivery to the Immune Synapse. Frontiers In Immunology 2019, 10: 700. PMID: 31031745, PMCID: PMC6470250, DOI: 10.3389/fimmu.2019.00700.Peer-Reviewed Original ResearchConceptsImmune synapsePlasma membraneSignaling eventsPhospholipid phosphatidylserineInner leafletPhosphatidic acidCellular responsesGranule deliveryCell functionImmune cell functionExtracellular changesFunction of cytotoxic T lymphocytesMembrane changesCytotoxic T lymphocytesMembraneSynapseCytoskeletonT lymphocytesActinPhosphoinositideDiacylglycerolPhosphatidylserineMessenger
2018
SHIP1 Inhibition As Novel Therapeutic Approach in Chronic Lymphocytic Leukemia
Ecker V, Braun M, Neumayer T, Muschen M, Ruland J, Buchner M. SHIP1 Inhibition As Novel Therapeutic Approach in Chronic Lymphocytic Leukemia. Blood 2018, 132: 894. DOI: 10.1182/blood-2018-99-117053.Peer-Reviewed Original ResearchChronic lymphocytic leukemiaMyeloid-derived suppressor cellsSecondary lymphoid organsImmune cell functionPeripheral bloodCLL cellsLymph nodesMalignant CLL cellsB cellsT cellsImmune responseLymphoid organsLymphocytic leukemiaSmall molecule inhibitorsSHIP1 inhibitionAge-matched healthy donorsAnti-tumor immune responsePharmacological inhibitionCell deathCLL peripheral bloodTreatment-related toxicityImmunoglobulin-producing plasma cellsRegulatory T cellsCell functionCLL cell deathFingolimod modulates T cell phenotype and regulatory T cell plasticity in vivo
Dominguez-Villar M, Raddassi K, Danielsen AC, Guarnaccia J, Hafler DA. Fingolimod modulates T cell phenotype and regulatory T cell plasticity in vivo. Journal Of Autoimmunity 2018, 96: 40-49. PMID: 30122421, PMCID: PMC7882197, DOI: 10.1016/j.jaut.2018.08.002.Peer-Reviewed Original ResearchConceptsT cellsMultiple sclerosisT cell effector phenotypeRelapsing-remitting multiple sclerosisRegulatory T cell populationTh1-like phenotypeRegulatory T cellsPro-inflammatory cytokinesT-cell phenotypeT cell populationsExpression of Th1Immune cell functionRegulatory T cell plasticityT cell plasticityCentral nervous systemExpression of markersCell migratory capacityImportant immunomodulatory functionsExcessive Th1Fingolimod treatmentExhaustion markersTh17 cytokinesEffector phenotypeLymph nodesSerum levels
2017
Enhanced TH17 Responses in Patients with IL10 Receptor Deficiency and Infantile-onset IBD
Shouval DS, Konnikova L, Griffith AE, Wall SM, Biswas A, Werner L, Nunberg M, Kammermeier J, Goettel JA, Anand R, Chen H, Weiss B, Li J, Loizides A, Yerushalmi B, Yanagi T, Beier R, Conklin LS, Ebens CL, Santos FGMS, Sherlock M, Goldsmith JD, Kotlarz D, Glover SC, Shah N, Bousvaros A, Uhlig HH, Muise AM, Klein C, Snapper SB. Enhanced TH17 Responses in Patients with IL10 Receptor Deficiency and Infantile-onset IBD. Inflammatory Bowel Diseases 2017, 23: 1950-1961. PMID: 29023267, DOI: 10.1097/mib.0000000000001270.Peer-Reviewed Original ResearchConceptsT cell proliferationDeficient patientsTh17 cellsReceptor deficiencySevere infantile-onset inflammatory bowel diseaseInfantile-onset inflammatory bowel diseaseAdaptive immune cell functionsCD4 T cell functionCD4 T cell proliferationCD4 T cell subsetsHematopoietic stem cell transplantationPeripheral blood mononuclear cellsNaive T cell proliferationSuppression of TregsGeneration of TregsInflammatory bowel diseaseRegulatory T cellsStem cell transplantationT cell subsetsBlood mononuclear cellsImmune cell defectsAnti-inflammatory macrophagesT cell functionImmune cell functionReal-time polymerase chain reactionAGE-RELATED CHANGES IN INNATE IMMUNE CELL FUNCTION
Montgomery R. AGE-RELATED CHANGES IN INNATE IMMUNE CELL FUNCTION. Innovation In Aging 2017, 1: 1254-1254. PMCID: PMC6183893, DOI: 10.1093/geroni/igx004.4559.Peer-Reviewed Original ResearchInnate immune cellsImmune cellsInnate immune cell functionLevels of TLR5Natural killer cellsToll-like receptorsImmune cell functionAge-Associated DecreasePotential therapeutic opportunitiesAge-related changesVaccine responsesKiller cellsVaccine strategiesOlder donorsImmune functionOlder subjectsTherapeutic opportunitiesInfectious diseasesProgressive declinePrimary humanCell functionMass cytometrySurface expressionReduced levelsReduced productionTAM receptor tyrosine kinases as emerging targets of innate immune checkpoint blockade for cancer therapy
Akalu YT, Rothlin CV, Ghosh S. TAM receptor tyrosine kinases as emerging targets of innate immune checkpoint blockade for cancer therapy. Immunological Reviews 2017, 276: 165-177. PMID: 28258690, PMCID: PMC5381815, DOI: 10.1111/imr.12522.BooksMeSH KeywordsAdaptive ImmunityAnimalsAntibodies, MonoclonalAxl Receptor Tyrosine Kinasec-Mer Tyrosine KinaseCostimulatory and Inhibitory T-Cell ReceptorsDrug Therapy, CombinationHumansImmunity, InnateImmunotherapyNeoplasmsProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSignal TransductionTumor EscapeConceptsCheckpoint blockadeAdaptive anti-tumor immune responsesT cell checkpoint blockadeT-cell checkpoint inhibitorsAnti-tumor immune responseInnate immune cell functionDendritic cell activityInnate immune checkpointImmune checkpoint blockadeSubset of patientsInnate immune cellsAnti-tumoral immunityProduction of chemokinesImmune cell functionMode of treatmentTAM receptor tyrosine kinasesTremendous clinical successCheckpoint inhibitorsImmune checkpointsCancer immunotherapyUnresponsive patientsImmune cellsT cellsImmune responseAdaptive immunityDOP082 Enhanced TH17 responses in patients with IL10 receptor deficiency and history of infantile-onset IBD
Shouval D, Konnikova L, Werner L, Nunberg M, Weiss B, Glover S, Snapper S. DOP082 Enhanced TH17 responses in patients with IL10 receptor deficiency and history of infantile-onset IBD. Journal Of Crohn's And Colitis 2017, 11: s75-s75. DOI: 10.1093/ecco-jcc/jjx002.119.Peer-Reviewed Original ResearchT cell proliferationGeneration of TregsTreg suppressionTh17 cellsCell functionCell proliferationIntestinal lamina propria cellsInnate immune cell functionHematopoietic stem cell transplantationRegulatory T cell functionPeripheral blood mononuclear cellsNaïve T cell proliferationEnhanced Th17 responseFrequency of CD4Regulatory T cellsStem cell transplantationT cell subsetsBlood mononuclear cellsHealthy control subjectsImmune cell defectsLamina propria cellsAnti-inflammatory macrophagesT cell functionImmune cell functionTh17 axis
2016
Multiple sclerosis
Axisa PP, Hafler DA. Multiple sclerosis. Current Opinion In Neurology 2016, 29: 345-353. PMID: 27058221, PMCID: PMC7882195, DOI: 10.1097/wco.0000000000000319.Peer-Reviewed Original ResearchConceptsMultiple sclerosisGenome-wide association studiesAssociation studiesMultiple sclerosis (MS) etiologyMultiple sclerosis progressionMultiple sclerosis patientsHigh-throughput genetic analysisImmune cell functionNumerous candidate biomarkersWide association studyMechanisms of neurodegenerationImmunomodulatory treatmentSclerosis patientsClinical outcomesTreatment arsenalDisease progressionImmune regulationSclerosisNew biomarkersCandidate biomarkersPatient careGenetic variationGenetic analysisCell functionProgression
2015
Bactericidal/Permeability-Increasing Protein Fold–Containing Family Member A1 in Airway Host Protection and Respiratory Disease
Britto CJ, Cohn L. Bactericidal/Permeability-Increasing Protein Fold–Containing Family Member A1 in Airway Host Protection and Respiratory Disease. American Journal Of Respiratory Cell And Molecular Biology 2015, 52: 525-534. PMID: 25265466, PMCID: PMC4491141, DOI: 10.1165/rcmb.2014-0297rt.BooksConceptsPulmonary diseaseHost protectionChronic obstructive pulmonary diseaseObstructive pulmonary diseaseIdiopathic pulmonary fibrosisMember A1Immune cell functionMultiple lung diseasesBactericidal/permeability-increasing proteinRespiratory malignanciesPulmonary pathogenesisPulmonary fibrosisPermeability-increasing proteinRespiratory secretionsLung diseaseUpper airwayRespiratory tractRespiratory diseaseProximal tracheaImmunomodulatory propertiesBPIFA1Cystic fibrosisDiseasePotential drug targetsEnvironmental exposures
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