2025
Selective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody Drug Conjugate TAK-500.
Appleman V, Matsuda A, Ganno M, Zhang D, Rosentrater E, Maldonado Lopez A, Porciuncula A, Hatten T, Christensen C, Merrigan S, Lee H, Lee M, Wang C, Dong L, Huang J, Iartchouk N, Wang J, Xu H, Yoneyama T, Piatkov K, Haridas S, Harbison C, Gregory R, Parent A, Lineberry N, Arendt C, Schalper K, Abu-Yousif A. Selective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody Drug Conjugate TAK-500. Cancer Immunology Research 2025 PMID: 39918395, DOI: 10.1158/2326-6066.cir-24-0103.Peer-Reviewed Original ResearchIntratumoral myeloid cellsMyeloid cellsTumor microenvironmentImmune responseCCR2+ cellsI interferonImmunosuppressive myeloid populationsImmune activation in vitroImmune cell markersLocal immune activationMurine tumor modelsAdaptive immune responsesAntibody drug conjugatesType I interferonAntitumor immunityInnate immune responseMyeloid populationsSTING agonistsSolid tumorsCCR2 proteinImmune activationTumor modelCell markersHuman tumorsAdaptive immunityTranslocating gut pathobiont Enterococcus gallinarum induces TH17 and IgG3 anti-RNA–directed autoimmunity in mouse and human
Gronke K, Nguyen M, Fuhrmann H, Santamaria de Souza N, Schumacher J, Pereira M, Löschberger U, Brinkhege A, Becker N, Yang Y, Sonnert N, Leopold S, Martin A, von Münchow-Klein L, Pessoa Rodrigues C, Cansever D, Hallet R, Richter K, Schubert D, Daniel G, Dylus D, Forkel M, Schwinge D, Schramm C, Redanz S, Lassen K, Manfredo Vieira S, Piali L, Palm N, Bieniossek C, Kriegel M. Translocating gut pathobiont Enterococcus gallinarum induces TH17 and IgG3 anti-RNA–directed autoimmunity in mouse and human. Science Translational Medicine 2025, 17: eadj6294. PMID: 39908347, DOI: 10.1126/scitranslmed.adj6294.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusAutoimmune diseasesToll-like receptor 8Gut pathobiontsHuman adaptive immune responseLong-term sequelaeAdaptive immune responsesHuman T cellsChronic autoimmune diseaseHuman monocyte activationContribution to autoimmunityAutoimmune hepatitisAutoantibody titersAnti-<i>E.Autoimmune pathophysiologyLupus modelT-helperLifelong immunosuppressionTargeted therapyT cellsDisease activityLupus erythematosusAutoantibody responseMonocyte activationImmune response
2024
Immunogenicity of cell death and cancer immunotherapy with immune checkpoint inhibitors
Catanzaro E, Beltrán-Visiedo M, Galluzzi L, Krysko D. Immunogenicity of cell death and cancer immunotherapy with immune checkpoint inhibitors. Cellular & Molecular Immunology 2024, 22: 24-39. PMID: 39653769, PMCID: PMC11685666, DOI: 10.1038/s41423-024-01245-8.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsImmunogenic cell deathImmunogenic cell death inducerCheckpoint inhibitorsRefractory to immune checkpoint inhibitorsImmunogenicity of cell deathFraction of patientsCombinatorial treatment strategiesAdaptive immune responsesCell deathCombinatorial partnersCancer immunotherapyCombinatorial regimensClinical findingsClinical managementTreatment strategiesClinical activityImmune responseImmunotherapyPatientsCancerOncology settingInhibitorsDeathInducerEpitope-anchored contrastive transfer learning for paired CD8+ T cell receptor–antigen recognition
Zhang Y, Wang Z, Jiang Y, Littler D, Gerstein M, Purcell A, Rossjohn J, Ou H, Song J. Epitope-anchored contrastive transfer learning for paired CD8+ T cell receptor–antigen recognition. Nature Machine Intelligence 2024, 6: 1344-1358. DOI: 10.1038/s42256-024-00913-8.Peer-Reviewed Original ResearchPeptide-major histocompatibility complexT cellsEpitope-specific T cellsImmune responseResidue-level interactionsPredicted binding strengthSpike-specific immune responsesTCR-based immunotherapyTumor-associated antigensT cell antigen recognitionPredicted binding specificityAdaptive immune responsesTCR cross-reactivityTCR repertoireCross-reactivityBinding specificityAutoimmune diseasesImmunodominant epitopesContact residuesAntigen recognitionHistocompatibility complexTCRImmunotherapyDistance matrixT-cell receptor-antigen recognitionChitinase 3-like-1 Inhibits Innate Antitumor and Tissue Remodeling Immune Responses by Regulating CD47-SIRPα- and CD24-Siglec10-Mediated Phagocytosis.
Ma B, Kamle S, Sadanaga T, Lee C, Lee J, Yee D, Zhu Z, Silverman E, DeMeo D, Choi A, Lee C, Elias J. Chitinase 3-like-1 Inhibits Innate Antitumor and Tissue Remodeling Immune Responses by Regulating CD47-SIRPα- and CD24-Siglec10-Mediated Phagocytosis. The Journal Of Immunology 2024, 213: 1279-1291. PMID: 39291933, DOI: 10.4049/jimmunol.2400035.Peer-Reviewed Original ResearchImmune checkpoint moleculesChronic obstructive pulmonary diseaseInhibit adaptive immune responsesAdaptive immune responsesInnate immune responseImmune responseInhibition of innate immune responsesInhibits T cell costimulationGeneration of adaptive immune responsesMacrophage phagocytosisInhibit innate immune responsesChitinase 3-like 1T cell costimulationEpithelial cell deathObstructive pulmonary diseaseCheckpoint moleculesPoor prognosisLung injuryInhibit macrophagesPulmonary diseaseCHI3L1Inflammation pathwaysCancerSHP-2 phosphataseCell deathCommensal microbiome and gastrointestinal mucosal immunity: Harmony and conflict with our closest neighbor
Tian K, Jing D, Lan J, Lv M, Wang T. Commensal microbiome and gastrointestinal mucosal immunity: Harmony and conflict with our closest neighbor. Immunity Inflammation And Disease 2024, 12: e1316. PMID: 39023417, PMCID: PMC11256888, DOI: 10.1002/iid3.1316.Peer-Reviewed Original ResearchConceptsMucosal immune networkMucosal immune systemImmune systemMaintenance of intestinal healthSite of pathogen invasionPresence of commensal microbiotaImmune responsePattern recognition receptorsGut mucosal immune systemAntigen-presenting cellsMucosal immune cellsGastrointestinal mucosal immunityGut-associated lymphoid tissuePathogen invasionCommensal microbiotaGut homeostasisMicrobial communitiesProtective immune responsesAdaptive immune responsesNon-self antigensCommensal bacteriaCommensal microbiomeIntestinal healthInflammatory bowel diseaseRecognition receptorsSpecific CD4+ T cell phenotypes associate with bacterial control in people who ‘resist’ infection with Mycobacterium tuberculosis
Sun M, Phan J, Kieswetter N, Huang H, Yu K, Smith M, Liu Y, Wang C, Gupta S, Obermoser G, Maecker H, Krishnan A, Suresh S, Gupta N, Rieck M, Acs P, Ghanizada M, Chiou S, Khatri P, Boom W, Hawn T, Stein C, Mayanja-Kizza H, Davis M, Seshadri C. Specific CD4+ T cell phenotypes associate with bacterial control in people who ‘resist’ infection with Mycobacterium tuberculosis. Nature Immunology 2024, 25: 1411-1421. PMID: 38997431, PMCID: PMC11291275, DOI: 10.1038/s41590-024-01897-8.Peer-Reviewed Original ResearchConceptsMtb-specific T cellsT cellsPriming of adaptive immune responsesMtb infectionCD4+ T cellsProgression to active tuberculosisIndividuals exposed to Mycobacterium tuberculosisT-cell biomarkersMtb-specific antigensLatent MTB infectionAdaptive immune responsesBacterial controlAssociated with lackActive tuberculosisClinical phenotypeMtb exposureImmune responseClinical testingSouth African adolescentsTh17Mycobacterium tuberculosisInfectionNegative resultsNonhuman primatesImmune primingDendritic cells in food allergy, treatment, and tolerance
Liu E, Yin X, Siniscalco E, Eisenbarth S. Dendritic cells in food allergy, treatment, and tolerance. Journal Of Allergy And Clinical Immunology 2024, 154: 511-522. PMID: 38971539, PMCID: PMC11414995, DOI: 10.1016/j.jaci.2024.06.017.Peer-Reviewed Original ResearchAntigen presenting cellsDendritic cellsFood allergyOral tolerancePresenting cellsAllergic sensitizationPeripheral T regulatory cellsDevelopment of oral toleranceGut dendritic cellsT regulatory cellsDendritic cell subsetsLimited treatment optionsAdaptive immune responsesFood immunotherapyEpicutaneous immunotherapyCell subsetsTolerogenic programAlarmin releaseTreatment optionsLangerhans cellsFood toleranceInnocuous antigensSurface markersInflammatory conditionsImmune responseCytofluorometric assessment of calreticulin exposure on CD38+ plasma cells from the human bone marrow
Beltrán-Visiedo M, Serrano-Del Valle A, Jiménez-Aldúan N, Soler-Agesta R, Naval J, Galluzzi L, Marzo I. Cytofluorometric assessment of calreticulin exposure on CD38+ plasma cells from the human bone marrow. Methods In Cell Biology 2024, 189: 189-206. PMID: 39393883, DOI: 10.1016/bs.mcb.2024.05.009.Peer-Reviewed Original ResearchCD38+ plasma cellsMultiple myelomaDendritic cellsBone marrowPlasma cellsProfessional antigen-presenting cellsBone marrow of patientsAssociated with improved disease outcomeMarrow of patientsAntigen-presenting cellsSurface of malignant cellsSurface of cancer cellsDying cellsAdaptive immune responsesChaperone calreticulinHuman bone marrowCalreticulin exposureEffector phaseMalignant cellsTolerogenic macrophagesExposure of phosphatidylserineImmunological memoryImmune responseClinical relevanceCancer cellsA novel microporous biomaterial vaccine platform for long-lasting antibody mediated immunity against viral infection
Mayer D, Nelson M, Andriyanova D, Filler R, Ökten A, Antao O, Chen J, Scumpia P, Weaver W, Wilen C, Deshayes S, Weinstein J. A novel microporous biomaterial vaccine platform for long-lasting antibody mediated immunity against viral infection. Journal Of Controlled Release 2024, 370: 570-582. PMID: 38734312, PMCID: PMC11665867, DOI: 10.1016/j.jconrel.2024.05.008.Peer-Reviewed Original ResearchAntigen delivery platformGerminal centersCD4<sup>+</sup> T follicular helper (Tfh) cellsT follicular helper (Tfh) cellsAdaptive immune cell responsesOptimal adaptive immune responsesAnti-receptor binding domain antibodiesInfluenza virus challengeRobust neutralizing antibodiesImmune cell responsesEnhanced neutralizing antibodiesAdaptive immune responsesDelivery platformAntibody mediated immunityLymph nodesVaccine platformNeutralizing antibodiesHumoral immunitySARS-CoV-2 spike proteinSustained release profileTarget antigenImmune responseVirus challengeViral infectionCell responsesImpact of immunotherapy time-of-day infusion on survival and immunologic correlates in patients with metastatic renal cell carcinoma: a multicenter cohort analysis
Patel J, Woo Y, Draper A, Jansen C, Carlisle J, Innominato P, Lévi F, Dhabaan L, Master V, Bilen M, Khan M, Lowe M, Kissick H, Buchwald Z, Qian D. Impact of immunotherapy time-of-day infusion on survival and immunologic correlates in patients with metastatic renal cell carcinoma: a multicenter cohort analysis. Journal For ImmunoTherapy Of Cancer 2024, 12: e008011. PMID: 38531662, PMCID: PMC10966813, DOI: 10.1136/jitc-2023-008011.Peer-Reviewed Original ResearchConceptsInfusions of immune checkpoint inhibitorsMetastatic renal cell carcinomaProgression-free survivalOverall survivalRenal cell carcinomaCell carcinomaInternational Metastatic RCC Database Consortium risk scoreAssociated with longer progression-free survivalLung cancerGroup BGroup ATime of ICI initiationLonger progression-free survivalNon-small cell lung cancerMultivariable Cox proportional hazards regressionImmune checkpoint inhibitorsPretreatment lactate dehydrogenaseCell lung cancerCox proportional hazards regressionAdaptive immune responsesProportional hazards regressionMulticenter cohort analysisCheckpoint inhibitorsICI initiationMetastatic melanomaImmunogenicity of ferroptosis in cancer: a matter of context?
Catanzaro E, Demuynck R, Naessens F, Galluzzi L, Krysko D. Immunogenicity of ferroptosis in cancer: a matter of context? Trends In Cancer 2024, 10: 407-416. PMID: 38368244, DOI: 10.1016/j.trecan.2024.01.013.Peer-Reviewed Original ResearchTumor-targeting immune responsesImmune responseCancer cellsKill malignant cellsAdaptive immune responsesInduction of ferroptosisImmunogenicity of ferroptosisAnticancer immunityMicroenvironmental defectMalignant cellsImmune cellsPlasma membrane breakdownFerroptosis inducersNecrotic formCell deathFerroptosisImbalance of cellular redox homeostasisLipid peroxidationCellsMembrane breakdownCellular redox homeostasisRedox homeostasisContext-dependent effectsImmunogenicityAdjuvanticityNon-mutational neoantigens in disease
Stern L, Clement C, Galluzzi L, Santambrogio L. Non-mutational neoantigens in disease. Nature Immunology 2024, 25: 29-40. PMID: 38168954, PMCID: PMC11075006, DOI: 10.1038/s41590-023-01664-1.Peer-Reviewed Original ResearchConceptsNon-canonical initiation codonsPost-translational protein modificationMature T cellsRibosomal RNA processingAlternative RNA splicingProtein-coding regionsNon-mutational mechanismsAbility of mammalsRNA processingRNA splicingInitiation codonProtein modificationHuman diseasesMature T cell repertoireAntigenic peptidesImmune recognitionAdaptive immune responsesT cellsAntigenic determinantsMHC class ICellsSplicingNovel antigenic determinantsMammalsCodon
2023
2368. 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 IgAMucosal immune alterations at the early onset of tissue destruction in chronic obstructive pulmonary disease
de Fays C, Geudens V, Gyselinck I, Kerckhof P, Vermaut A, Goos T, Vermant M, Beeckmans H, Kaes J, Van Slambrouck J, Mohamady Y, Willems L, Aversa L, Cortesi E, Hooft C, Aerts G, Aelbrecht C, Everaerts S, McDonough J, De Sadeleer L, Gohy S, Ambroise J, Janssens W, Ceulemans L, Van Raemdonck D, Vos R, Hackett T, Hogg J, Kaminski N, Gayan-Ramirez G, Pilette C, Vanaudenaerde B. Mucosal immune alterations at the early onset of tissue destruction in chronic obstructive pulmonary disease. Frontiers In Immunology 2023, 14: 1275845. PMID: 37915582, PMCID: PMC10616299, DOI: 10.3389/fimmu.2023.1275845.Peer-Reviewed Original ResearchConceptsCD8+ T cell accumulationT cell accumulationImmune alterationsTerminal bronchiolesTissue destructionCOPD lungsCD4+ T cellsMyeloid antigen-presenting cellsAntigen-presenting cellsSmall airway changesTissue destructive processesChronic airway inflammationInnate immune alterationsB cell activationMucosal immune defenseAdaptive immune responsesChronic obstructive pulmonary diseaseObstructive pulmonary diseaseIncreased mucus productionAlveolar surface densityAirway changesT cellsAirway inflammationImmune cellsB cellsLeishmania major-derived lipophosphoglycan influences the host’s early immune response by inducing platelet activation and DKK1 production via TLR1/2
Ihedioha O, Sivakoses A, Beverley S, McMahon-Pratt D, Bothwell A. Leishmania major-derived lipophosphoglycan influences the host’s early immune response by inducing platelet activation and DKK1 production via TLR1/2. Frontiers In Immunology 2023, 14: 1257046. PMID: 37885890, PMCID: PMC10598878, DOI: 10.3389/fimmu.2023.1257046.Peer-Reviewed Original ResearchConceptsLeukocyte-platelet aggregatesEarly immune responseImmune responsePlatelet activationHost's early immune responseCell-mediated immune responsesTh2 cell polarizationAdaptive immune responsesPro-inflammatory responsePattern recognition receptorsKey virulence factorsRecognition receptorsInfectious diseasesPathogenic moleculesEndothelial cellsWnt antagonistsInfection siteVirulence factorsTLR1/2PlateletsDickkopf1Cell typesLipophosphoglycanActivationResponseElevated glucose metabolism driving pro-inflammatory response in B cells contributes to the progression of type 1 diabetes
Li Z, Zhao M, Li J, Luo W, Huang J, Huang G, Xie Z, Xiao Y, Huang J, Li X, Zhao B, Zhou Z. Elevated glucose metabolism driving pro-inflammatory response in B cells contributes to the progression of type 1 diabetes. Clinical Immunology 2023, 255: 109729. PMID: 37562723, DOI: 10.1016/j.clim.2023.109729.Peer-Reviewed Original ResearchConceptsType 1 diabetesPro-inflammatory responseB cellsGlucose metabolismCytokine productionAberrant B cell responsesNon-obese diabetic (NOD) micePro-inflammatory cytokine productionHigh blood glucose levelsOnset of diabetesInflammatory cytokine productionAdaptive immune responsesB cell responsesCross-sectional cohortImmune system failureDiabetic mouse modelB cell functionBlood glucose levelsB cell populationsB cell metabolismPancreatic beta cellsB cell proliferationElevated glucose metabolismInsulitis developmentNOD miceBSBM-16 HLA CLASS-I ANTIGEN PRESENTATION MACHINERY AND IFN-γ PATHWAY ALTERATIONS IN LUNG CANCER BRAIN METASTASES
Vilarino N, de Rodas M, Lu B, Goldberg S, Schalper K. BSBM-16 HLA CLASS-I ANTIGEN PRESENTATION MACHINERY AND IFN-γ PATHWAY ALTERATIONS IN LUNG CANCER BRAIN METASTASES. Neuro-Oncology Advances 2023, 5: iii4-iii4. PMCID: PMC10402438, DOI: 10.1093/noajnl/vdad070.012.Peer-Reviewed Original ResearchLung cancer brain metastasesPrimary lung tumorsImmune checkpoint inhibitorsCancer brain metastasesBrain metastasesPresentation machineryClinicopathologic variablesHLA classTumor cell PD-L1 expressionBackground Immune checkpoint inhibitorsLocal adaptive immune responseHLA Class I AntigenPD-L1 expressionDuration of responseB2MAdaptive immune responsesDistinct immunomodulatory propertiesImmune evasion mechanismsClass I AntigenIFN-γ signalingIRF-1Interferon regulatory factor 1Checkpoint inhibitorsMost patientsWorse survivalCombinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.
Krykbaeva I, Bridges K, Damsky W, Pizzurro G, Alexander A, McGeary M, Park K, Muthusamy V, Eyles J, Luheshi N, Turner N, Weiss S, Olino K, Kaech S, Kluger H, Miller-Jensen K, Bosenberg M. Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance. Cancer Immunology Research 2023, 11: 1332-1350. PMID: 37478171, DOI: 10.1158/2326-6066.cir-22-0699.Peer-Reviewed Original ResearchConceptsPD-1 resistanceDendritic cellsTumor regressionAnti-PD-1 resistanceActivates Dendritic CellsCytokine secretion profilingSystemic cytokine profileTriple therapy combinationInnate immune activationAdaptive immune responsesComplete tumor regressionMajority of miceSignificant clinical challengeMouse melanoma modelT cell activationAgonistic CD40Checkpoint inhibitorsDC subsetsTriple therapyCytokine profileImmune activationCombinatorial immunotherapyTherapy combinationsT cellsClinical challengeSREBP2 regulates the endothelial response to cytokines via direct transcriptional activation of KLF6
Fowler J, Boutagy N, Zhang R, Horikami D, Whalen M, Romanoski C, Sessa W. SREBP2 regulates the endothelial response to cytokines via direct transcriptional activation of KLF6. Journal Of Lipid Research 2023, 64: 100411. PMID: 37437844, PMCID: PMC10407908, DOI: 10.1016/j.jlr.2023.100411.Peer-Reviewed Original ResearchConceptsDirect transcriptional activationTranscriptional activationEndothelial cellsChemokine expressionChromatin immunoprecipitation sequencingCholesterol homeostasisSterol-responsive genesPro-inflammatory chemokinesLipid-lowering drugsAdaptive immune responsesPro-inflammatory genesTranscription factor SREBP2Endogenous cholesterol synthesisImmunoprecipitation sequencingResponsive genesMechanism of actionPromoter regionCardiovascular riskAtherosclerotic diseaseInflammatory phenotypeImmune modulationCardiovascular diseaseImmune responseInflammatory stimuliI interferon
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