2025
A phase 1 study of durvalumab as monotherapy or combined with tremelimumab with or without azacitidine in patients with myelodysplastic syndrome
Garcia-Manero G, Gaddh M, Platzbecker U, Lindsley R, Larson S, Chevassut T, Fenaux P, Komrokji R, Lyons R, Al-Kali A, Jiang Y, Bothos J, Townsley D, Zeidan A. A phase 1 study of durvalumab as monotherapy or combined with tremelimumab with or without azacitidine in patients with myelodysplastic syndrome. Annals Of Hematology 2025, 104: 1577-1585. PMID: 40153010, PMCID: PMC12031784, DOI: 10.1007/s00277-024-06081-4.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsDose-limiting toxicityPhase 1 studyPD-L1Adverse eventsUpregulation of programmed death ligand 1Marrow complete responseDeath-ligand 1Hypomethylating agent treatmentPrimary safety endpointProgression to AMLEvaluation of clinical outcomesComplete responseHematologic improvementIWG criteriaMyelodysplastic syndromeOpen-labelSecondary endpointsSafety endpointsClinical outcomesLimited efficacyPatientsLigand 1Agent treatmentOverall response
2024
Platelet–Monocyte Aggregate Instigates Inflammation and Vasculopathy in Kawasaki Disease
Zhang Y, Jia C, Guo M, Chen Q, Wen Y, Wang T, Xie Y, Fan X, Gao J, Yarovinsky T, Liu R, Jiang Z, Wang M, Zhou J, Che D, Fu L, Edelson R, Gu X, Hwa J, Tang W. Platelet–Monocyte Aggregate Instigates Inflammation and Vasculopathy in Kawasaki Disease. Advanced Science 2024, 12: 2406282. PMID: 39665236, PMCID: PMC11792051, DOI: 10.1002/advs.202406282.Peer-Reviewed Original ResearchKawasaki diseaseCD14<sup>+</sup>CD16<sup>+</sup> monocytesPlatelet-monocyte aggregatesAberrant immune responseAcute febrile illnessCoronary artery aneurysmsNuclear factor-kappaBSystemic vasculitisPlatelet-monocyteProinflammatory monocytesPlatelet hyperreactivityArtery aneurysmVasculopathyFebrile illnessCytokine mediatorsHyperactive plateletsReduce inflammationPlatelet glycoproteinImmune responseInterleukin-1Platelet activationPositive feedback loopLigand 1MonocytesGrowth factorScoring PD-L1 Expression in Urothelial Carcinoma: An International Multi-Institutional Study on Comparison of Manual and Artificial Intelligence Measurement Model (AIM-PD-L1) Pathology Assessments
Rüschoff J, Kumar G, Badve S, Jasani B, Krause E, Rioux-Leclercq N, Rojo F, Martini M, Cheng L, Tretiakova M, Mitchell C, Anders R, Robert M, Fahy D, Pyle M, Le Q, Yu L, Glass B, Baxi V, Babadjanova Z, Pratt J, Brutus S, Karasarides M, Hartmann A. Scoring PD-L1 Expression in Urothelial Carcinoma: An International Multi-Institutional Study on Comparison of Manual and Artificial Intelligence Measurement Model (AIM-PD-L1) Pathology Assessments. Virchows Archiv 2024, 484: 597-608. PMID: 38570364, DOI: 10.1007/s00428-024-03795-8.Peer-Reviewed Original ResearchConceptsPD-L1 expressionImmune checkpoint inhibitorsPD-L1Tumor cellsAssess programmed death ligand 1Assessment of PD-L1 expressionScoring of PD-L1 expressionInternational multi-institutional studyPD-L1 expression analysisFood and Drug Administration-approvedPD-L1 stainingDeath-ligand 1Drug Administration-approvedMulti-institutional studyCheckpoint inhibitorsUrothelial carcinomaPathological assessmentBiomarker expressionInterobserver variabilityLigand 1Cancer treatmentExpert pathologistsClinical settingMultinational studyPositive rate
2022
Proceedings From the ASCO/College of American Pathologists Immune Checkpoint Inhibitor Predictive Biomarker Summit.
Hayes D, Herbst R, Myles J, Topalian S, Yohe S, Aronson N, Bellizzi A, Basu Roy U, Bradshaw G, Edwards R, El-Gabry E, Elvin J, Gajewski T, McShane L, Oberley M, Philip R, Rimm D, Rosenbaum J, Rubin E, Schlager L, Sherwood S, Stewart M, Taube J, Thurin M, Vasalos P, Laser J. Proceedings From the ASCO/College of American Pathologists Immune Checkpoint Inhibitor Predictive Biomarker Summit. JCO Precision Oncology 2022, 6: e2200454. PMID: 36446042, PMCID: PMC10530621, DOI: 10.1200/po.22.00454.Peer-Reviewed Original ResearchConceptsICI therapyImmune checkpoint inhibition therapyDeath ligand 1 (PD-L1) expressionMultiple predictive biomarkersTumor biomarker testsCheckpoint inhibition therapyLigand 1 expressionDeath ligand 1Field of oncologyICI benefitPredictive factorsPredictive biomarkersInhibition therapyNeoantigen expressionBiomarker testsHealth insurance organizationsUS FoodDrug AdministrationAmerican PathologistsMedicaid ServicesTherapyBiomarker developmentNational InstituteLigand 1Clinical applicationPembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study
Harrington KJ, Burtness B, Greil R, Soulières D, Tahara M, de Castro G, Psyrri A, Brana I, Basté N, Neupane P, Bratland Å, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Ishak W, Lin J, Gumuscu B, Swaby RF, Rischin D. Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Journal Of Clinical Oncology 2022, 41: 790-802. PMID: 36219809, PMCID: PMC9902012, DOI: 10.1200/jco.21.02508.Peer-Reviewed Original ResearchConceptsPD-L1 CPSNeck squamous cell carcinomaSquamous cell carcinomaRecurrent/metastatic headMetastatic headCell carcinomaOverall survivalNext-line therapyObjective response ratePembrolizumab-based therapyProgression-free survivalDeath ligand 1Long-term efficacyKEYNOTE-048Data cutoffSurvival benefitTotal populationMedian studyPembrolizumabResponse rateCarcinomaPositive scoreLigand 1Subsequent treatmentEfficacyAdaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities
Kim TK, Vandsemb EN, Herbst RS, Chen L. Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities. Nature Reviews Drug Discovery 2022, 21: 529-540. PMID: 35701637, DOI: 10.1038/s41573-022-00493-5.Peer-Reviewed Original ResearchConceptsAdaptive immune resistanceImmune resistanceCell death 1 ligand 1Tumor siteDeath 1 ligand 1Anti-PD therapyBlockade of PDL1Advanced-stage cancerFraction of patientsStrong mechanistic rationaleFuture drug developmentCurrent cancer therapiesImmune attackClinical trialsSolid tumorsTherapeutic opportunitiesTumorsCancer therapySelective inductionAntitumour drugsLigand 1Drug developmentTherapyAdditive effectMechanistic rationaleDENR controls JAK2 translation to induce PD-L1 expression for tumor immune evasion
Chen B, Hu J, Hu X, Chen H, Bao R, Zhou Y, Ye Y, Zhan M, Cai W, Li H, Li HB. DENR controls JAK2 translation to induce PD-L1 expression for tumor immune evasion. Nature Communications 2022, 13: 2059. PMID: 35440133, PMCID: PMC9018773, DOI: 10.1038/s41467-022-29754-y.Peer-Reviewed Original ResearchConceptsPD-L1 expressionTumor immune evasionImmune evasionReduced PD-L1 expressionDeath ligand 1Tumor-killing activityT cellsTherapeutic targetTumor growthCancer cellsCRISPR/Cas9 screeningLigand 1Cell homeostasisKinase 2ExpressionEvasionCD8ImmunotherapyCellsIFNγDysfunctionRBP dysfunctionTumorsCancerGraded Prognostic Assessment (GPA) for Patients With Lung Cancer and Brain Metastases: Initial Report of the Small Cell Lung Cancer GPA and Update of the Non-Small Cell Lung Cancer GPA Including the Effect of Programmed Death Ligand 1 and Other Prognostic Factors
Sperduto PW, De B, Li J, Carpenter D, Kirkpatrick J, Milligan M, Shih HA, Kutuk T, Kotecha R, Higaki H, Otsuka M, Aoyama H, Bourgoin M, Roberge D, Dajani S, Sachdev S, Gainey J, Buatti JM, Breen W, Brown PD, Ni L, Braunstein S, Gallitto M, Wang TJC, Shanley R, Lou E, Shiao J, Gaspar LE, Tanabe S, Nakano T, An Y, Chiang V, Zeng L, Soliman H, Elhalawani H, Cagney D, Thomas E, Boggs DH, Ahluwalia MS, Mehta MP. Graded Prognostic Assessment (GPA) for Patients With Lung Cancer and Brain Metastases: Initial Report of the Small Cell Lung Cancer GPA and Update of the Non-Small Cell Lung Cancer GPA Including the Effect of Programmed Death Ligand 1 and Other Prognostic Factors. International Journal Of Radiation Oncology • Biology • Physics 2022, 114: 60-74. PMID: 35331827, PMCID: PMC9378572, DOI: 10.1016/j.ijrobp.2022.03.020.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerSmall cell lung cancerGraded Prognostic AssessmentBrain metastasesSignificant prognostic factorsPrognostic factorsDeath ligand 1Cell lung cancerLung cancerPD-L1Lung adenocarcinomaMedian survivalNSCLC adenocarcinomaPrognostic assessmentInitial reportMulti-institutional retrospective databaseProgrammed Death Ligand 1PD-L1 1Tumor molecular statusOverall median survivalPD-L1 expressionLigand 1Anaplastic lymphoma kinaseEpidermal growth factor receptorGrowth factor receptor
2020
Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function
Zhang Y, Aldo P, You Y, Ding J, Kaislasuo J, Petersen JF, Lokkegaard E, Peng G, Paidas MJ, Simpson S, Pal L, Guller S, Liu H, Liao AH, Mor G. Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function. Journal Of Leukocyte Biology 2020, 108: 983-998. PMID: 32386458, PMCID: PMC8190653, DOI: 10.1002/jlb.1a0420-012rr.Peer-Reviewed Original ResearchConceptsSoluble PD-L1Macrophage polarizationTrophoblast cellsCell death ligand 1PD-L1/PDPD-1 blockageDeath ligand 1Macrophage differentiationModulates macrophage polarizationExpression/secretionDecidual macrophagesHealthy pregnancyPD-L1Pregnant womenTLR4 ligationM2 phenotypeExpression of typeFetal developmentLPS activationMacrophagesIFNPlacenta developmentLigand 1Constitutive productionGestationPlatelet P-selectin initiates cross-presentation and dendritic cell differentiation in blood monocytes
Han P, Hanlon D, Arshad N, Lee JS, Tatsuno K, Yurter A, Robinson E, Filler R, Sobolev O, Cote C, Rivera-Molina F, Toomre D, Fahmy T, Edelson R. Platelet P-selectin initiates cross-presentation and dendritic cell differentiation in blood monocytes. Science Advances 2020, 6: eaaz1580. PMID: 32195350, PMCID: PMC7065880, DOI: 10.1126/sciadv.aaz1580.Peer-Reviewed Original ResearchConceptsDendritic cellsDifferentiation of monocytesBlood monocytesTumor-specific T cell immunityCytokine-derived DCsT cell immunityAntigen-specific immunityPlatelet P-selectinDendritic cell differentiationPeripheral blood monocytesCell immunityP-selectin glycoprotein ligand-1P-selectinExogenous cytokinesNuclear factorMonocytesPhysiologic maturationPhysiological mannerCalcium fluxingNuclear localizationLigand 1Cell differentiationImmunityRapid maturationPlatelets
2019
Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced, Programmed Death Ligand 1–Expressing NSCLC
Barlesi F, Garon E, Kim D, Felip E, Han J, Kim J, Ahn M, Fidler M, Gubens M, de Castro G, Surmont V, Li Q, Deitz A, Lubiniecki G, Herbst R. Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced, Programmed Death Ligand 1–Expressing NSCLC. Journal Of Thoracic Oncology 2019, 14: 793-801. PMID: 30711649, DOI: 10.1016/j.jtho.2019.01.016.Peer-Reviewed Original ResearchConceptsGlobal health statusDeath ligand 1Composite endpointPhase II/III studyGHS/QoL scoresLife Questionnaire Core 30Programmed Death Ligand 1Symptom domainsNSCLC patient populationPembrolizumab-treated patientsWeek 12 changesHealth-related qualityLigand 1Quality of lifeGHS/KEYNOTE-010Advanced NSCLCChest painIII studyOverall survivalCancer QualityEuroQol-5D.Life scoresMean baselinePatient population
2018
PD-L1 binds to B7-1 only in cis on the same cell surface
Chaudhri A, Xiao Y, Klee A, Wang X, Zhu B, Freeman G. PD-L1 binds to B7-1 only in cis on the same cell surface. Cancer Immunology Research 2018, 6: canimm.0316.2017. PMID: 29871885, PMCID: PMC7394266, DOI: 10.1158/2326-6066.cir-17-0316.Peer-Reviewed Original ResearchConceptsPD-L1PD-1B7-1Tumor-infiltrating myeloid cellsB7-1 interactionPD-L1 bindsSoluble PD-1Death ligand 1T cell functionPD-L1 bindingPeripheral toleranceTumor immunotherapyCancer immunotherapyCell binding assaysImmune attackMyeloid cellsSame cellsSuch coexpressionSame cell surfaceLigand 1ImmunotherapyCD28Further investigationELISACytometry
2017
A Quantitative Comparison of Antibodies to Programmed Cell Death 1 Ligand 1
Gaule P, Smithy JW, Toki M, Rehman J, Patell-Socha F, Cougot D, Collin P, Morrill P, Neumeister V, Rimm DL. A Quantitative Comparison of Antibodies to Programmed Cell Death 1 Ligand 1. JAMA Oncology 2017, 3: 256-259. PMID: 27541827, PMCID: PMC5491359, DOI: 10.1001/jamaoncol.2016.3015.Peer-Reviewed Original ResearchPD-L1 expressionPD-L1Tissue microarrayImmunohistochemical analysisCell death 1 ligand 1PD-1 axis inhibitorsDeath 1 ligand 1Quantitative immunofluorescenceCell linesPredictive diagnostic testsTumor tissue coresPD-L1 proteinPrediction of responseYale Pathology archivesLung cancerClinical utilityPathology archivesDiagnostic testsMonoclonal antibodiesAntibodiesTissue controlsProtein levelsTissue coresLigand 1Concordant results
2016
Inverse correlation of soluble programmed cell death-1 ligand-1 (sPD-L1) with eosinophil count and clinical severity in allergic rhinitis patients
Kalmarzi R, Fattahi N, Kaviani Z, Ataee P, Mansouri M, Moradi G, Yousefzade A, Abbassi J. Inverse correlation of soluble programmed cell death-1 ligand-1 (sPD-L1) with eosinophil count and clinical severity in allergic rhinitis patients. Allergology International 2016, 66: 326-331. PMID: 27617656, DOI: 10.1016/j.alit.2016.08.008.Peer-Reviewed Original ResearchConceptsProgrammed cell death 1 ligand 1Eosinophil countAllergic rhinitisDisease severityCell death 1 ligand 1Serum soluble PD-L1Modified allergic rhinitisSoluble PD-L1Co-signaling moleculesInverse correlationAllergic rhinitis patientsSeverity of ARRhinitis patientsT cellsAutoimmune disordersClinical severityAR progressionWhole blood samplesTherapeutic approachesAllergic diseasesLigand 1PatientsSevere diseaseBlood samplesEosinophilsPD-L1 Expression in Lung Cancer
Yu H, Boyle TA, Zhou C, Rimm D, Hirsch FR. PD-L1 Expression in Lung Cancer. Journal Of Thoracic Oncology 2016, 11: 964-975. PMID: 27117833, PMCID: PMC5353357, DOI: 10.1016/j.jtho.2016.04.014.Peer-Reviewed Original ResearchConceptsPD-L1Lung cancerAnti-PD-1 drugsDifferent PD-L1 antibodiesPD-L1 protein expressionImmunotherapy clinical trialsAdvanced lung cancerPD-L1 expressionPD-L1 antibodiesSubset of patientsDeath ligand 1PD-L1 detectionBetter patient careClinical trialsPatient careProtein expressionHistory of useImmunohistochemistry platformBiomarkersImmunotherapyLigand 1PatientsCancerExpressionTrials
2014
Prospects for targeting PD-1 and PD-L1 in various tumor types.
Kim JW, Eder JP. Prospects for targeting PD-1 and PD-L1 in various tumor types. Oncology 2014, 28 Suppl 3: 15-28. PMID: 25387682.Peer-Reviewed Original Research
2013
Sarcomatoid Lung Carcinomas Show High Levels of Programmed Death Ligand-1 (PD-L1)
Velcheti V, Rimm DL, Schalper KA. Sarcomatoid Lung Carcinomas Show High Levels of Programmed Death Ligand-1 (PD-L1). Journal Of Thoracic Oncology 2013, 8: 803-805. PMID: 23676558, PMCID: PMC3703468, DOI: 10.1097/jto.0b013e318292be18.Peer-Reviewed Original ResearchConceptsDeath ligand 1Sarcomatoid carcinomaCell lung carcinomaLung carcinomaPD-L1PD-1/PD-L1 axisPD-1/PD-L1 pathwayProgrammed Death Ligand 1PD-L1 protein expressionEffector immune responsesPD-L1 axisPD-L1 pathwayLung sarcomatoid carcinomaLung cancer cohortSarcomatoid lung carcinomasLigand 1Mouse monoclonal antibodyDeath-1Lymphocytic infiltrationRare subtypeSuch therapyCancer cohortT cellsCarcinomaTumor types
2010
Absence of P-Selectin in Recipients of Allogeneic Bone Marrow Transplantation Ameliorates Experimental Graft-versus-Host Disease
Lu S, Holland A, Na I, Terwey T, Alpdogan O, Bautista J, Smith O, Suh D, King C, Kochman A, Hubbard V, Rao U, Yim N, Liu C, Laga A, Murphy G, Jenq R, Zakrzewski J, Penack O, Dykstra L, Bampoe K, Perez L, Furie B, Furie B, van den Brink M. Absence of P-Selectin in Recipients of Allogeneic Bone Marrow Transplantation Ameliorates Experimental Graft-versus-Host Disease. The Journal Of Immunology 2010, 185: 1912-1919. PMID: 20622117, PMCID: PMC3752704, DOI: 10.4049/jimmunol.0903148.Peer-Reviewed Original ResearchConceptsSecondary lymphoid organsDonor T cellsAllogeneic bone marrow transplantationAlloreactive T cellsBone marrow transplantationT cellsWT T cellsP-selectinP-selectin glycoprotein ligand-1P-selectin ligandsMarrow transplantationSmall bowelInflamed tissuesDonor alloreactive T cellsHost disease (GVHD) pathophysiologyGVHD target organsAlloactivated T cellsLigand 1Wild-type recipientsGVHD mortalityGVHD prophylaxisHost diseaseLymphoid organsPeyer's patchesExperimental disease
2009
Bcl6 is required for the development of T follicular helper cells marked by downregulation of P-selectin glycoprotein ligand-1 (46.7)
Poholek A, Hernandez S, Chandele A, Dong X, Odegard J, Kaech S, Dent A, Craft J. Bcl6 is required for the development of T follicular helper cells marked by downregulation of P-selectin glycoprotein ligand-1 (46.7). The Journal Of Immunology 2009, 182: 46.7-46.7. DOI: 10.4049/jimmunol.182.supp.46.7.Peer-Reviewed Original ResearchTfh cellsP-selectin glycoprotein ligand-1IL-21PD-1T cellsFollicular helper T cellsAbsence of ICOSExpression of CXCR5Follicular helper cellsTfh cell developmentHelper T cellsLigand 1B cell maturationTranscriptional repressor BCL6ICOS signalingNew surface markersHelper cellsGerminal centersB cellsCell maturationSurface markersExpression of BCL6BCL6CXCR5Downregulation
2008
ICOS-dependent extrafollicular helper T cells elicit IgG production via IL-21 in systemic autoimmunity
Odegard JM, Marks BR, DiPlacido LD, Poholek AC, Kono DH, Dong C, Flavell RA, Craft J. ICOS-dependent extrafollicular helper T cells elicit IgG production via IL-21 in systemic autoimmunity. Journal Of Experimental Medicine 2008, 205: 2873-2886. PMID: 18981236, PMCID: PMC2585848, DOI: 10.1084/jem.20080840.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, Differentiation, T-LymphocyteAutoimmunityCell DifferentiationChemokinesDisease Models, AnimalGerminal CenterImmunoglobulin Class SwitchingImmunoglobulin GInducible T-Cell Co-Stimulator ProteinInterleukinsLupus Erythematosus, SystemicMembrane GlycoproteinsMiceMice, KnockoutPlasma CellsReceptors, CXCR4T-Lymphocyte SubsetsT-Lymphocytes, Helper-InducerConceptsEffector T cellsT cellsIL-21IgG productionCXC chemokine receptor 4 (CXCR4) expressionB cell helper functionFollicular helper T cellsChemokine receptor 4 expressionReceptor 4 expressionCD4 T cellsHelper T cellsMRL/MpJAutoimmune strainsP-selectin glycoprotein ligand-1Autoantibody productionChronic autoimmunitySystemic autoimmunityPlasma cellsExtrafollicular responseExtrafollicular sitesMouse modelGerminal centersHelper functionSelective lossLigand 1
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