2025
Progressive natural killer cell dysfunction in advanced-stage clear-cell renal cell carcinoma and association with clinical outcomes
Xu W, Birch G, Meliki A, Moritz V, Bharadwaj M, Schindler N, Labaki C, Saliby R, Dinh K, Horst J, Sun M, Kashima S, Hugaboom M, Dighe A, Machaalani M, Lee G, Hurwitz M, McGregor B, Hirsch M, Shukla S, McDermott D, Signoretti S, Romee R, Choueiri T, Braun D. Progressive natural killer cell dysfunction in advanced-stage clear-cell renal cell carcinoma and association with clinical outcomes. ESMO Open 2025, 10: 104105. PMID: 39813824, PMCID: PMC11783098, DOI: 10.1016/j.esmoop.2024.104105.Peer-Reviewed Original ResearchConceptsClear-cell renal cell carcinomaAdvanced clear-cell renal cell carcinomaNK cell phenotypeNK cell functionNK cellsRenal cell carcinomaClinical outcomesCell carcinomaCell phenotypeRestoration of NK cell functionNormal kidneyNatural killer (NK) cellsMarkers of tissue residencyNatural killer cell dysfunctionAssociated with worse overall survivalClear-cell renal cell carcinoma patientsLocalized clear-cell renal cell carcinomaTumor-infiltrating NK cellsAnalyzed single-cell RNA sequencing dataAssociated with worse survivalExpression of cytotoxic genesPaired normal kidneyLocal tumor extensionNK cell subsetsPrimary tumor specimens
2024
In vivo AAV–SB-CRISPR screens of tumor-infiltrating primary NK cells identify genetic checkpoints of CAR-NK therapy
Peng L, Renauer P, Sferruzza G, Yang L, Zou Y, Fang Z, Park J, Chow R, Zhang Y, Lin Q, Bai M, Sanchez A, Zhang Y, Lam S, Ye L, Chen S. In vivo AAV–SB-CRISPR screens of tumor-infiltrating primary NK cells identify genetic checkpoints of CAR-NK therapy. Nature Biotechnology 2024, 43: 752-761. PMID: 38918616, PMCID: PMC11668911, DOI: 10.1038/s41587-024-02282-4.Peer-Reviewed Original ResearchPrimary NK cellsTumor-infiltrating NKCAR-NK cellsNK cellsGenetic checkpointsNatural killerChimeric antigen receptor (CAR)-NK cellsHuman primary NK cellsSolid tumor mouse modelNK cell-based immunotherapyIn vivo antitumor efficacyCAR-NK therapyNK cell therapyCell-based immunotherapyNK cell functionTumor mouse modelTumor infiltrationAntitumor efficacyCell therapyCytokine productionEnhanced cytotoxicityMouse modelSingle-cell transcriptomic landscapeClinical potentialCell function
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
2020
From Chickens to Humans: The Importance of Peptide Repertoires for MHC Class I Alleles
Kaufman J. From Chickens to Humans: The Importance of Peptide Repertoires for MHC Class I Alleles. Frontiers In Immunology 2020, 11: 601089. PMID: 33381122, PMCID: PMC7767893, DOI: 10.3389/fimmu.2020.601089.Peer-Reviewed Original ResearchConceptsKiller immunoglobulin-like receptorsMajor histocompatibility complexPeptide motifsClass I moleculesCytotoxic T lymphocytesCell surfaceChicken major histocompatibility complexClass I allelesBinding peptidesI moleculesNatural killerClassical class I moleculesResistance to infectious diseasesMultigene familyRepertoire of bound peptidesI allelesThymus-derived (T) cellsReceptor-ligand interactionsNK cell functionImmunoglobulin-like receptorsPeptide-bindingMajor histocompatibility complex class I allelePeptide repertoireAllelesMHC-I molecules
2017
The Abl‐1 Kinase is Dispensable for NK Cell Inhibitory Signalling and is not Involved in Murine NK Cell Education
Ganesan S, Luu TT, Chambers BJ, Meinke S, Brodin P, Vivier E, Wetzel DM, Koleske AJ, Kadri N, Höglund P. The Abl‐1 Kinase is Dispensable for NK Cell Inhibitory Signalling and is not Involved in Murine NK Cell Education. Scandinavian Journal Of Immunology 2017, 86: 135-142. PMID: 28605050, PMCID: PMC5568956, DOI: 10.1111/sji.12574.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, LyCell DifferentiationCells, CulturedCytotoxicity, ImmunologicImmunity, InnateInterferon-gammaKiller Cells, NaturalLymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutNatural Cytotoxicity Triggering Receptor 1NK Cell Lectin-Like Receptor Subfamily CProto-Oncogene Proteins c-ablSignal TransductionConceptsNK cell educationNK cellsCell educationNatural killer cell responsivenessYAC-1 tumor cellsNK cell inhibitionNK cell functionHuman NK cellsMurine NK cellsMHC class IC-AblC-Abl expressionInhibitory Ly49Normal inhibitoryNKG2A receptorsInhibitory receptorsCell responsivenessReceptor stimulationReceptor repertoireInhibitory signalingTumor cellsITAM receptorsClass ICell inhibitionCell functionIdentification of differentially expressed genes associated with clinical response after treatment of breast cancer skin metastases with imiquimod.
Rozenblit M, Heguy A, Chiriboga L, Loomis C, Darvishian F, Egeblad M, Shao Y, Adams S. Identification of differentially expressed genes associated with clinical response after treatment of breast cancer skin metastases with imiquimod. Journal Of Clinical Oncology 2017, 35: e12541-e12541. DOI: 10.1200/jco.2017.35.15_suppl.e12541.Peer-Reviewed Original ResearchBreast cancer skin metastasesSkin metastasesClinical responseImiquimod treatmentInnate immunityNK cellsT cellsB cellsToll-like receptor 7 agonistAnti-tumor immune responseER/PR statusPanCancer Immune Profiling PanelUpregulation of genesReceptor 7 agonistNK cell functionImmune Profiling PanelPossible combination therapiesUpregulation of TNFGene expression changesActivation of lymphocytesExpression changesTop upregulated genesPrediction of responseIL-17Non respondersCanonical and cross-reactive binding of NK cell inhibitory receptors to HLA-C allotypes is dictated by peptides bound to HLA-C
Sim M, Malaker S, Khan A, Stowell J, Shabanowitz J, Peterson M, Rajagopalan S, Hunt D, Altmann D, Long E, Boyton R. Canonical and cross-reactive binding of NK cell inhibitory receptors to HLA-C allotypes is dictated by peptides bound to HLA-C. The Journal Of Immunology 2017, 198: 222.25-222.25. DOI: 10.4049/jimmunol.198.supp.222.25.Peer-Reviewed Original ResearchKiller cell Ig-like receptorsHLA-C allotypesCross-reactive bindingHuman NK cell activityNK cell inhibitory receptorsNK cell activityNK cell functionInhibitory killer cell Ig-like receptorsNK cell activationDisorders of pregnancyCell inhibitory receptorsIg-like receptorsInhibitory receptorsHLA genotypeKIR2DL1-C2Viral infectionHLACell activationCell activityKIR2DL1Cell functionEndogenous peptidesPotential mechanismsDisease associationsSpecific bindingBrain Ischemia Suppresses Immunity in the Periphery and Brain via Different Neurogenic Innervations
Liu Q, Jin WN, Liu Y, Shi K, Sun H, Zhang F, Zhang C, Gonzales RJ, Sheth KN, La Cava A, Shi FD. Brain Ischemia Suppresses Immunity in the Periphery and Brain via Different Neurogenic Innervations. Immunity 2017, 46: 474-487. PMID: 28314594, DOI: 10.1016/j.immuni.2017.02.015.Peer-Reviewed Original ResearchConceptsPost-stroke infectionsBrain ischemiaMiddle cerebral artery occlusionCell-mediated immune defenseAdrenal axis leadsNK cell numbersCerebral artery occlusionNK cell responsesNK cell functionNatural killer cellsExpression of SOCS3Infectious complicationsArtery occlusionImmune alterationsIschemic strokeSplenic atrophyKiller cellsImmune functionCell responsesGenetic ablationIschemiaImmune defenseBrainCell functionInnervationCanonical and Cross-reactive Binding of NK Cell Inhibitory Receptors to HLA-C Allotypes Is Dictated by Peptides Bound to HLA-C
Sim MJ, Malaker SA, Khan A, Stowell JM, Shabanowitz J, Peterson ME, Rajagopalan S, Hunt DF, Altmann DM, Long EO, Boyton RJ. Canonical and Cross-reactive Binding of NK Cell Inhibitory Receptors to HLA-C Allotypes Is Dictated by Peptides Bound to HLA-C. Frontiers In Immunology 2017, 8: 193. PMID: 28352266, PMCID: PMC5348643, DOI: 10.3389/fimmu.2017.00193.Peer-Reviewed Original ResearchKiller cell immunoglobulin-like receptorsImpact of HLAHLA-C allotypesCross-reactive bindingHLA-C allelesHuman natural killer cell activityInhibitory killer cell immunoglobulin-like receptorsNatural killer cell activityNK cell inhibitory receptorsHIV Gag peptidesKiller cell activityNK cell functionNK cell activationNK cell biologyEndogenous peptidesDisorders of pregnancyImmunoglobulin-like receptorsCell inhibitory receptorsSpecific bindingKIR specificityGag peptidesInhibitory receptorsHLA genotypeKIR-HLAPeptide dependence
2015
Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo
Das R, Verma R, Sznol M, Boddupalli CS, Gettinger SN, Kluger H, Callahan M, Wolchok JD, Halaban R, Dhodapkar MV, Dhodapkar KM. Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo. The Journal Of Immunology 2015, 194: 950-959. PMID: 25539810, PMCID: PMC4380504, DOI: 10.4049/jimmunol.1401686.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, SurfaceAntineoplastic Combined Chemotherapy ProtocolsCTLA-4 AntigenCytokinesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunophenotypingIpilimumabLymphocytes, Tumor-InfiltratingNeoplasmsNivolumabProgrammed Cell Death 1 ReceptorSignal TransductionT-Lymphocyte SubsetsConceptsPD-1T cellsCTLA-4Checkpoint blockadeCombination therapyReceptor occupancyCombination immune checkpoint blockadeCTLA-4 immune checkpointsPD-1 receptor occupancyTransitional memory T cellsAnti-PD-1 therapyAnti CTLA-4Immune-based combinationsPD-1 blockadeSoluble IL-2RImmune checkpoint blockadeNK cell functionMemory T cellsTherapy-induced changesT cell activationTumor T cellsHuman T cellsRemarkable antitumor effectImmunologic changesImmunologic effects
2004
TLR9 Agonist Immunomodulator Treatment of Cutaneous T-Cell Lymphoma (CTCL) with CPG7909.
Kim Y, Girardi M, Duvic M, Kuzel T, Rook A, Link B, Pinter-Brown L, Comerci C, McAuley S, Schmalbach T. TLR9 Agonist Immunomodulator Treatment of Cutaneous T-Cell Lymphoma (CTCL) with CPG7909. Blood 2004, 104: 743. DOI: 10.1182/blood.v104.11.743.743.Peer-Reviewed Original ResearchCutaneous T-cell lymphomaCPG 7909Progressive diseaseClinical responseStable diseasePartial responseComplete responseAdvanced cutaneous T-cell lymphomaModerate flu-like symptomsGlobal assessmentLocal injection site reactionsCTC grade 1More systemic therapiesObjective clinical responsesPhysician global assessmentDurability of responseFlu-like symptomsInjection site reactionsNK cell functionPhase II portionWeeks of treatmentResults of patientsT-cell lymphomaGamma-glutamyl transferaseImmunomodulator treatment
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