2022
A Comparison of Murine PD-1 and PD-L1 Monoclonal Antibodies
Bu M, Yuan L, Klee A, Freeman G. A Comparison of Murine PD-1 and PD-L1 Monoclonal Antibodies. Monoclonal Antibodies In Immunodiagnosis And Immunotherapy 2022, 41: 202-209. PMID: 35925787, PMCID: PMC9451140, DOI: 10.1089/mab.2021.0068.Peer-Reviewed Original ResearchConceptsPD-1Cancer immunotherapyMouse modelPD-L1 monoclonal antibodiesPD-L1/PDMonoclonal antibodiesEffective cancer immunotherapyAntibody effector activityMouse PD-1Murine PD-1PD-L1Novel agentsEffector activityTherapeutic monoclonal antibodiesImmunotherapyEpitope recognitionMAbsAntibodiesHigh affinityBlockadePathwayBiological activity
2021
Spatial signatures identify immune escape via PD-1 as a defining feature of T-cell/histiocyte-rich large B-cell lymphoma
Griffin GK, Weirather JL, Roemer MGM, Lipschitz M, Kelley A, Chen PH, Gusenleitner D, Jeter E, Pak C, Gjini E, Chapuy B, Rosenthal MH, Xu J, Chen BJ, Sohani AR, Lovitch SB, Abramson JS, Ishizuka J, Kim AI, Jacobson CA, LaCasce AS, Fletcher CD, Neuberg D, Freeman GJ, Hodi FS, Wright K, Ligon AH, Jacobsen ED, Armand P, Shipp MA, Rodig SJ. Spatial signatures identify immune escape via PD-1 as a defining feature of T-cell/histiocyte-rich large B-cell lymphoma. Blood 2021, 137: 1353-1364. PMID: 32871584, PMCID: PMC8555417, DOI: 10.1182/blood.2020006464.Peer-Reviewed Original ResearchConceptsT-cell/histiocyte-rich large B-cell lymphomaLarge B-cell lymphomaB-cell lymphomaMalignant B cellsDiffuse large B-cell lymphomaClassic Hodgkin lymphomaPD-1B cellsImmune signaturesImmune escapePD-1/PD-L1 pathwayPD-L1/PDImmune escape pathwayPD-1 blockadeImmune cell infiltratesPD-L1 expressionRefractory hematologic malignanciesPD-L1 pathwayMulti-institutional cohortClinical responsePartial responseCell infiltrateComplete responsePD-L1Aggressive variant
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 productionGestationO81 IMpower110: interim overall survival (OS) analysis of a phase III study of atezolizumab (ATEZO) monotherapy vs platinum-based chemotherapy (CHEMO) as first-line (1L) treatment in PD-L1–selected NSCLC
Herbst R, De Marinis F, Giaccone G, Reinmuth N, Vergnenegre A, Barrios C, Morise M, Font E, Andric Z, Geater S, Ozguroglu M, Mocci S, McCleland M, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, Jassem J, Spigel D. O81 IMpower110: interim overall survival (OS) analysis of a phase III study of atezolizumab (ATEZO) monotherapy vs platinum-based chemotherapy (CHEMO) as first-line (1L) treatment in PD-L1–selected NSCLC. Journal For ImmunoTherapy Of Cancer 2020, 8: a1. DOI: 10.1136/lba2019.1.Peer-Reviewed Original ResearchTreatment-related AEsPD-L1 expressionPrimary endpointArm APD-L1Interim overall survival analysisTumor PD-L1 statusPD-L1/PDCarboplatin AUC 6ECOG PS 0Primary efficacy populationUnexpected safety signalsFirst-line treatmentPD-L1 statusPhase III studyPlatinum-based chemotherapyWT populationOverall survival analysisDeclaration of HelsinkiAttractive treatment choiceAtezolizumab monotherapyAUC 5AUC 6CPI monotherapyECOG PS
2019
LBA78 IMpower110: Interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1–selected NSCLC
Spigel D, de Marinis F, Giaccone G, Reinmuth N, Vergnenegre A, Barrios C, Morise M, Felip E, Andric Z, Geater S, Özgüroğlu M, Mocci S, McCleland M, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, Jassem J, Herbst R. LBA78 IMpower110: Interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1–selected NSCLC. Annals Of Oncology 2019, 30: v915. DOI: 10.1093/annonc/mdz293.Peer-Reviewed Original ResearchTreatment-related AEsPD-L1 expressionPD-L1F. Hoffmann-La RocheBristol-Myers SquibbHoffmann-La RocheBoehringer IngelheimArm ACisplatin 75mg/m2Interim overall survival analysisTumor PD-L1 statusTumor-infiltrating immune cellsPD-L1/PDEli LillyCarboplatin AUC 6ECOG PS 0Primary efficacy populationUnexpected safety signalsPD-L1 statusFirst-line treatmentPhase III studyPlatinum-based chemotherapyOverall survival analysisRoche/GenentechBristol-Meyers Squibb
2017
Perspectives in immunotherapy: meeting report from the “Immunotherapy Bridge”, Napoli, November 30th 2016
Ascierto PA, Daniele B, Hammers H, Hirsh V, Kim J, Licitra L, Nanda R, Pignata S. Perspectives in immunotherapy: meeting report from the “Immunotherapy Bridge”, Napoli, November 30th 2016. Journal Of Translational Medicine 2017, 15: 205. PMID: 29020960, PMCID: PMC5637331, DOI: 10.1186/s12967-017-1309-2.Peer-Reviewed Original ResearchConceptsTypes of cancerAnti-PD-1/PD-L1 monotherapyPlatinum-refractory metastatic urothelial carcinomaResponse rateImmune systemPD-L1/PDFirst-line monotherapyImmunotherapy-responsive diseasePD-L1 monotherapyPre-treated NSCLCAddition of chemotherapyDiscontinuation of therapyMetastatic urothelial carcinomaMetastatic breast cancerUse of nivolumabMetastatic renal carcinomaImmune checkpoint receptorsModest response ratesHigh response rateLess side effectsMultiple oncogenic pathwaysImmunotherapy BridgeLine monotherapyAdvanced NSCLCMetastatic NSCLCMUC1 inhibition leads to decrease in PD-L1 levels via upregulation of miRNAs
Pyzer AR, Stroopinsky D, Rosenblatt J, Anastasiadou E, Rajabi H, Washington A, Tagde A, Chu JH, Coll M, Jiao AL, Tsai LT, Tenen DE, Cole L, Palmer K, Ephraim A, Leaf RK, Nahas M, Apel A, Bar-Natan M, Jain S, McMasters M, Mendez L, Arnason J, Raby BA, Slack F, Kufe D, Avigan D. MUC1 inhibition leads to decrease in PD-L1 levels via upregulation of miRNAs. Leukemia 2017, 31: 2780-2790. PMID: 28555079, PMCID: PMC5791150, DOI: 10.1038/leu.2017.163.Peer-Reviewed Original ResearchConceptsPD-L1 expressionAcute myeloid leukemiaAML cellsMiR-200cPD-L1/PDT cell-mediated lysisPD-L1 mRNA levelsLeukemia-specific T cellsPD-L1 levelsAnti-tumor immunityImmunosuppressive tumor microenvironmentMurine AML modelHuman AML cellsAML cell linesPotential therapeutic targetMicroRNA miR-200cMiR-34a levelsNanostring arraysMyeloid leukemiaT cellsTherapeutic targetMUC1 inhibitionTumor microenvironmentAML modelUpregulation of miRNAs
2016
RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors
Loi S, Dushyanthen S, Beavis PA, Salgado R, Denkert C, Savas P, Combs S, Rimm DL, Giltnane JM, Estrada MV, Sánchez V, Sanders ME, Cook RS, Pilkinton MA, Mallal SA, Wang K, Miller VA, Stephens PJ, Yelensky R, Doimi FD, Gómez H, Ryzhov SV, Darcy PK, Arteaga CL, Balko JM. RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors. Clinical Cancer Research 2016, 22: 1499-1509. PMID: 26515496, PMCID: PMC4794351, DOI: 10.1158/1078-0432.ccr-15-1125.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB7-H1 AntigenBiomarkersCell Line, TumorDisease Models, AnimalDisease ProgressionFemaleGene Expression ProfilingHumansImmunomodulationImmunophenotypingLymphocytes, Tumor-InfiltratingMiceMitogen-Activated Protein KinasesMortalityPhenotypeProgrammed Cell Death 1 ReceptorProtein Kinase Inhibitorsras ProteinsSignal TransductionTranscriptomeTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerTumor-infiltrating lymphocytesImmune checkpoint inhibitorsResidual diseaseNeoadjuvant chemotherapyBreast cancerPD-L1Checkpoint inhibitorsMHC expressionMouse modelPD-1/PD-L1 immune checkpoint inhibitorsPD-L1 immune checkpoint inhibitorsPresence of TILsPD-1/PD-L1Low tumor-infiltrating lymphocytesPD-L1/PDAntitumor immune responseRAS/MAPK activationCell-surface MHC expressionMAPK activationImproved survivalImproved prognosisPredictive biomarkersClinical trialsImmune responseIMvigor 210, a phase II trial of atezolizumab (MPDL3280A) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC).
Hoffman-Censits J, Grivas P, Van Der Heijden M, Dreicer R, Loriot Y, Retz M, Vogelzang N, Perez-Gracia J, Rezazadeh A, Bracarda S, Yu E, Hoimes C, Bellmunt J, Quinn D, Petrylak D, Hussain S, Cui N, Mariathasan S, Abidoye O, Rosenberg J. IMvigor 210, a phase II trial of atezolizumab (MPDL3280A) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC). Journal Of Clinical Oncology 2016, 34: 355-355. DOI: 10.1200/jco.2016.34.2_suppl.355.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaPoor prognostic factorPrognostic factorsPD-L1Prognostic subgroupsPD-L1/PDImmune cell statusMedian treatment durationPD-L1 subgroupsTreatment-related AEsPD-L1 expressionPD-L1 statusPhase II trialPlatinum-based chemotherapyCo-primary endpointsPoor prognostic subgroupMUC patientsRECIST v1.1Data cutoffDurable responsesII trialAntitumor immunityG3-4Median ageHistoric controls
2015
Clinical activity, safety, and biomarkers of MPDL3280A in metastatic urothelial bladder cancer: Additional analysis from phase IA study.
Kim J, Bellmunt J, Powles T, Loriot Y, Vogelzang N, Cruz Zambrano C, Burris H, Teng S, Shen X, Bruey J, Boyd Z, Hegde P, Petrylak D. Clinical activity, safety, and biomarkers of MPDL3280A in metastatic urothelial bladder cancer: Additional analysis from phase IA study. Journal Of Clinical Oncology 2015, 33: 297-297. DOI: 10.1200/jco.2015.33.7_suppl.297.Peer-Reviewed Original ResearchUrothelial bladder cancerMetastatic urothelial bladder cancerPD-L1 expressionBladder cancerImmune-mediated antitumor responsePD-L1/PDPhase Ia studyTreatment-related AEsTreatment-related deathsTumor burden markersTumor gene expressionIHC 0/1Median DORPrior platinumPt ageRECIST v1.1Median PFSPrior therapyData cutoffDurable responsesExpansion cohortInflammatory markersLiver metastasesPD-L1Antitumor response
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