2025
Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients
Chen J, Levy A, Tian A, Huang X, Cai G, Fidelle M, Rauber C, Ly P, Pizzato E, Sitterle L, Piccinno G, Liu P, Durand S, Mao M, Zhao L, Iebba V, Felchle H, Mallard de La Varende A, Fischer J, Thomas S, Greten T, Jones J, Monge C, Demaria S, Formenti S, Belluomini L, Dionisi V, Massard C, Blanchard P, Robert C, Quevrin C, Lopes E, Clémenson C, Mondini M, Meziani L, Zhan Y, Zeng C, Cai Q, Morel D, Sun R, Laurent P, Mangoni M, Di Cataldo V, Arilli C, Trommer M, Wegen S, Neppl S, Riechelmann R, Camandaroba M, Neto E, Fournier P, Segata N, Holicek P, Galluzzi L, Buqué A, Alves Costa Silva C, Derosa L, Kroemer G, Chen C, Zitvogel L, Deutsch E. Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients. Cancer Cell 2025, 43: 361-379.e10. PMID: 40068595, PMCID: PMC11907695, DOI: 10.1016/j.ccell.2025.02.010.Peer-Reviewed Original ResearchConceptsPD-L1 blockadeLow-dose irradiationCancer patientsAbscopal effectEfficacy of PD-L1 blockadeCD8<sup>+</sup> T cell activationBenefit of immune checkpoint inhibitorsClinical benefit of immune checkpoint inhibitorsTumor-draining lymph nodesSecond-line immunotherapyImmune checkpoint inhibitorsPhase 2 studyProspective clinical trialTumor-bearing miceCohort of cancer patientsT cell activationMetastatic cancer patientsAnti-cancer efficacyCheckpoint inhibitorsLocal radiotherapyPD-L1Clinical benefitLymph nodesOptimal dosimetryRetrospective cohort
2023
An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis
LaMarche N, Hegde S, Park M, Maier B, Troncoso L, Le Berichel J, Hamon P, Belabed M, Mattiuz R, Hennequin C, Chin T, Reid A, Reyes-Torres I, Nemeth E, Zhang R, Olson O, Doroshow D, Rohs N, Gomez J, Veluswamy R, Hall N, Venturini N, Ginhoux F, Liu Z, Buckup M, Figueiredo I, Roudko V, Miyake K, Karasuyama H, Gonzalez-Kozlova E, Gnjatic S, Passegué E, Kim-Schulze S, Brown B, Hirsch F, Kim B, Marron T, Merad M. An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis. Nature 2023, 625: 166-174. PMID: 38057662, PMCID: PMC11189607, DOI: 10.1038/s41586-023-06797-9.Peer-Reviewed Original ResearchConceptsInterleukin-4IL-4RαMyeloid cellsCheckpoint blockadeTumor burdenPD-1/PD-L1 checkpoint blockadePD-1/PD-L1 blockadeBone marrowTumor-infiltrating CD8 T cellsType 2 cytokines interleukin-4PD-L1 checkpoint blockadeCell lung cancer lesionsNon-small cell lung cancer lesionsDepletion of basophilsPD-L1 blockadePrimary disease siteCD8 T cellsImmune checkpoint blockadeLung cancer lesionsNovel combination therapiesCytokine interleukin-4Bone marrow basophilsConditional knockout miceRefractory NSCLCEarly myeloid progenitors
2022
Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer.
Shafi S, Aung T, Xirou V, Gavrielatou N, Vathiotis I, Fernandez A, Moutafi M, Yaghoobi V, Herbst R, Liu L, Langermann S, Rimm D. Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer. Laboratory Investigation 2022, 102: 1143-1149. PMID: 36775354, DOI: 10.1038/s41374-022-00796-6.Peer-Reviewed Original ResearchConceptsSiglec-15 expressionNon-small cell lung cancerNeck squamous cell carcinomaProgression-free survivalSquamous cell carcinomaCancer typesOverall survivalCell carcinomaBladder cancerImmune cellsSiglec-15PD-1/PD-L1 blockadePotential future clinical trialsQuantitative immunofluorescencePD-L1 blockadeStromal immune cellsImmune checkpoint blockadeCell lung cancerFuture clinical trialsNew potential targetsCheckpoint blockadePD-L1Lung cancerClinical trialsIntra-tumoral heterogeneityQuantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer
Shafi S, Aung TN, Xirou V, Gavrielatou N, Vathiotis IA, Fernandez A, Moutafi M, Yaghoobi V, Herbst RS, Liu LN, Langermann S, Rimm DL. Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer. Laboratory Investigation 2022, 102: 1143-1149. PMID: 35581307, PMCID: PMC10211373, DOI: 10.1038/s41374-022-00796-6.Peer-Reviewed Original ResearchConceptsSiglec-15 expressionNon-small cell lung cancerNeck squamous cell carcinomaProgression-free survivalSquamous cell carcinomaCancer typesOverall survivalCell carcinomaBladder cancerImmune cellsSiglec-15PD-1/PD-L1 blockadePotential future clinical trialsQuantitative immunofluorescencePD-L1 blockadeStromal immune cellsImmune checkpoint blockadeCell lung cancerFuture clinical trialsNew potential targetsCheckpoint blockadePD-L1Lung cancerClinical trialsIntra-tumoral heterogeneityDevelopment of an immunohistochemical assay for Siglec-15
Shafi S, Aung TN, Robbins C, Zugazagoitia J, Vathiotis I, Gavrielatou N, Yaghoobi V, Fernandez A, Niu S, Liu LN, Cusumano ZT, Leelatian N, Cole K, Wang H, Homer R, Herbst RS, Langermann S, Rimm DL. Development of an immunohistochemical assay for Siglec-15. Laboratory Investigation 2022, 102: 771-778. PMID: 35459795, PMCID: PMC9253057, DOI: 10.1038/s41374-022-00785-9.Peer-Reviewed Original ResearchConceptsSiglec-15IHC assaysPD-L1PD-1/PD-L1 inhibitionPD-L1 blockadePD-L1 inhibitionHigh expressionFuture clinical trialsImmunoglobulin-type lectinsSiglec-15 expressionCompanion diagnostic assayPromising new targetTumor histologyImmunotherapeutic targetLung cancerImmune cellsClinical trialsNovel recombinant antibodiesCancer histologyImmunohistochemical assaysMyeloid cellsTumor typesScoring systemNew targetsHigh concordance
2021
516 Peripheral and tumoral immune activity in the expansion part of the first-in-human DuoBody®-PD-L1×4–1BB (GEN1046) trial
Aix S, Calvo E, Moreno V, Garralda E, Cervantes A, Ramalingam S, Pérez J, LoRusso P, Furqan M, Cho D, Muik A, Lagkadinou E, Türeci Ö, Couto S, Pencheva N, Forssmann U, Şahin U, Ahmadi T, Higgs B, Jure-Kunkel M, Melero I. 516 Peripheral and tumoral immune activity in the expansion part of the first-in-human DuoBody®-PD-L1×4–1BB (GEN1046) trial. Journal For ImmunoTherapy Of Cancer 2021, 9: a546-a546. DOI: 10.1136/jitc-2021-sitc2021.516.Peer-Reviewed Original ResearchPrior anti-PD-1 therapyAnti-PD-1 therapyPD-L1NK cellsTumor reductionAnti-PD-1 combination therapyEffector memory T cellsPD-L1 blockadePhase 1/2a trialPrior systemic therapySoluble immune mediatorsTumor PD-L1Disease control rateAdvanced solid tumorsAntitumor immune responseSubset of patientsMemory T cellsSerial blood samplesImproved clinical efficacyTumor biopsy specimensCycle 1Tumor biopsy samplesEthics committees/institutional review boardsInstitutional review boardCycle 2539 Phase 1 study of mRNA-2752, a lipid nanoparticle encapsulating mRNAs encoding human OX40L/IL-23/IL-36γ, for intratumoral (ITu) injection +/- durvalumab in advanced solid tumors and lymphoma
Patel M, Jimeno A, Wang D, Stemmer S, Bauer T, Sweis R, Geva R, Kummar S, Reagan P, Perets R, LoRusso P, Gupta S, Zacharek S, Laino A, Milberg O, Frederick J, Chen S, Pascarella S, Randolph W, Aanur P, Johansen L, Do K, Meehan R, Sullivan R. 539 Phase 1 study of mRNA-2752, a lipid nanoparticle encapsulating mRNAs encoding human OX40L/IL-23/IL-36γ, for intratumoral (ITu) injection +/- durvalumab in advanced solid tumors and lymphoma. 2021, a569-a569. DOI: 10.1136/jitc-2021-sitc2021.539.Peer-Reviewed Original ResearchIL-23 serum concentrationsTreatment-emergent adverse eventsPro-inflammatory cytokinesIL-23IL-36γArm BSerum concentrationsAST/ALT increasePD-L1 inhibitor durvalumabPost-treatment tumor biopsiesSquamous cell bladder cancerPK/PD modelingEmergent adverse eventsPain/swellingPD-L1 blockadeCytokine release syndromeAdvanced solid tumorsCytokine IL-22PD-L1 levelsPhase 1 studyPK/PD modelT cell infiltrationEthics BoardGood clinical practiceTreatment effectsCross-talk of four types of RNA modification writers defines tumor microenvironment and pharmacogenomic landscape in colorectal cancer
Chen H, Yao J, Bao R, Dong Y, Zhang T, Du Y, Wang G, Ni D, Xun Z, Niu X, Ye Y, Li HB. Cross-talk of four types of RNA modification writers defines tumor microenvironment and pharmacogenomic landscape in colorectal cancer. Molecular Cancer 2021, 20: 29. PMID: 33557837, PMCID: PMC7869236, DOI: 10.1186/s12943-021-01322-w.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorColorectal NeoplasmsCombined Modality TherapyComputational BiologyDisease ManagementDisease SusceptibilityEpithelial-Mesenchymal TransitionGene Expression ProfilingGene Expression Regulation, NeoplasticHumansLymphocytes, Tumor-InfiltratingPharmacogeneticsPrognosisProportional Hazards ModelsRNA Processing, Post-TranscriptionalTranscription, GeneticTranscriptomeTumor MicroenvironmentConceptsColorectal cancerConsensus molecular subtypesTumor microenvironmentRNA modification patternsTME cell-infiltrating characteristicsWorse patient overall survivalDevelopment of CRCInhibitory immune cellsPD-L1 blockadeEfficacy of immunotherapyCharacteristics of TMEPatients' overall survivalPotential clinical utilityTherapeutic liabilityOverall survivalClinical featuresClinical benefitPatient survivalImmune cellsM2 macrophagesCRC samplesImmune responseMolecular subtypesClinical utilitySurvival advantage
2020
Bempegaldesleukin (NKTR-214) plus Nivolumab in Patients with Advanced Solid Tumors: Phase I Dose-Escalation Study of Safety, Efficacy, and Immune Activation (PIVOT-02)
Diab A, Tannir NM, Bentebibel SE, Hwu P, Papadimitrakopoulou V, Haymaker C, Kluger HM, Gettinger SN, Sznol M, Tykodi SS, Curti BD, Tagliaferri MA, Zalevsky J, Hannah AL, Hoch U, Aung S, Fanton C, Rizwan A, Iacucci E, Liao Y, Bernatchez C, Hurwitz ME, Cho DC. Bempegaldesleukin (NKTR-214) plus Nivolumab in Patients with Advanced Solid Tumors: Phase I Dose-Escalation Study of Safety, Efficacy, and Immune Activation (PIVOT-02). Cancer Discovery 2020, 10: 1158-1173. PMID: 32439653, DOI: 10.1158/2159-8290.cd-19-1510.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCarcinoma, Renal CellFemaleGene Expression Regulation, NeoplasticHumansImmune Checkpoint InhibitorsImmunotherapyInterleukin-2Kidney NeoplasmsLung NeoplasmsLymphocyte CountLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedNivolumabPolyethylene GlycolsProgrammed Cell Death 1 ReceptorTreatment OutcomeYoung AdultConceptsTreatment-related adverse eventsAdvanced solid tumorsPD-L1 statusSolid tumorsGrade 3/4 treatment-related adverse eventsPD-1/PD-L1 blockadeCommon treatment-related adverse eventsPhase I dose-escalation trialPoor prognostic risk factorsTotal objective response rateI dose-escalation studyI dose-escalation trialLongitudinal tumor biopsiesPD-L1 blockadeT-cell enhancementTreatment-related deathsObjective response ratePhase II doseDose-escalation studyDose-escalation trialDose-limiting toxicityFlu-like symptomsPrognostic risk factorsTumor-infiltrating lymphocytesCytotoxicity of CD8Differential effects of PD-L1 versus PD-1 blockade on myeloid inflammation in human cancer
Bar N, Costa F, Das R, Duffy A, Samur M, McCachren S, Gettinger S, Neparidze N, Parker TL, Bailur JK, Pendleton K, Bajpai R, Zhang L, Xu ML, Anderson T, Giuliani N, Nooka A, Cho HJ, Raval A, Shanmugam M, Dhodapkar KM, Dhodapkar M. Differential effects of PD-L1 versus PD-1 blockade on myeloid inflammation in human cancer. JCI Insight 2020, 5 PMID: 32427579, PMCID: PMC7406262, DOI: 10.1172/jci.insight.129353.Peer-Reviewed Original ResearchConceptsPD-L1 blockadePD-1 blockadeAsymptomatic multiple myelomaMonocyte-derived DCsPD-L1Immunologic effectsT cellsMyeloid cellsAntigen-specific T cell expansionAnti-PD-1 therapyMyeloid antigen-presenting cellsDistinct inflammatory signatureSystemic immunologic effectsLung cancer patientsT cell expansionAntigen-presenting cellsMyeloid activationMyeloid inflammationInflammatory signatureNIH/NCICheckpoint blockadeDC maturationL1 therapyCombination therapyInflammatory phenotypeDefining tumor resistance to PD-1 pathway blockade: recommendations from the first meeting of the SITC Immunotherapy Resistance Taskforce
Kluger HM, Tawbi HA, Ascierto ML, Bowden M, Callahan MK, Cha E, Chen HX, Drake CG, Feltquate DM, Ferris RL, Gulley JL, Gupta S, Humphrey RW, LaVallee TM, Le DT, Hubbard-Lucey VM, Papadimitrakopoulou VA, Postow MA, Rubin EH, Sharon E, Taube JM, Topalian SL, Zappasodi R, Sznol M, Sullivan RJ. Defining tumor resistance to PD-1 pathway blockade: recommendations from the first meeting of the SITC Immunotherapy Resistance Taskforce. Journal For ImmunoTherapy Of Cancer 2020, 8: e000398. PMID: 32238470, PMCID: PMC7174063, DOI: 10.1136/jitc-2019-000398.Peer-Reviewed Original ResearchConceptsCancer immunotherapyClinical definitionNew agentsPD-1/PD-L1 blockadePD-1 pathway blockadeConsensus clinical definitionPD-L1 blockadeDeath receptor-1Immunotherapy of cancerStandard of careClinical trial designTreatment discontinuationMechanisms of resistancePathway blockadeClinical trialsConfirmatory scanPrimary resistancePatient benefitSecondary resistanceTrial designTreatment approachesUnmet needReceptor 1Tumor resistancePattern of response
2019
Programmed Death-1 or Programmed Death Ligand-1 Blockade in Patients with Platinum-resistant Metastatic Urothelial Cancer: A Systematic Review and Meta-analysis
Niglio S, Jia R, Ji J, Ruder S, Patel V, Martini A, Sfakianos J, Marqueen K, Waingankar N, Mehrazin R, Wiklund P, Oh W, Mazumdar M, Ferket B, Galsky M. Programmed Death-1 or Programmed Death Ligand-1 Blockade in Patients with Platinum-resistant Metastatic Urothelial Cancer: A Systematic Review and Meta-analysis. European Urology 2019, 76: 782-789. PMID: 31200951, DOI: 10.1016/j.eururo.2019.05.037.Peer-Reviewed Original ResearchConceptsPD-1/PD-L1 inhibitorsMetastatic urothelial cancerPD-L1 blockadePD-1PD-1/PD-L1PD-L1Death-1Urothelial cancerSurvival outcomesPatients treated with PD-1/PD-L1 inhibitorsAnti-programmed death-ligand 1Follow-upPatients treated with PD-1Programmed death ligand 1 blockadeClinical trialsProgrammed death-ligand 1 inhibitorAnti-programmed death-1PD-1/PD-L1 blockadeSurvival dataAnti-PD-1Assessed PD-1PD-L1 inhibitorsProgrammed death-1Death-ligand 1PD-L1 inhibitionGenomic and Immune Profiling of a Patient With Triple-Negative Breast Cancer That Progressed During Neoadjuvant Chemotherapy Plus PD-L1 Blockade
Casadevall D, Li X, Powles RL, Wali VB, Buza N, Pelekanou V, Dhawan A, Foldi J, Szekely B, Lopez-Giraldez F, Hatzis C, Pusztai L. Genomic and Immune Profiling of a Patient With Triple-Negative Breast Cancer That Progressed During Neoadjuvant Chemotherapy Plus PD-L1 Blockade. JCO Precision Oncology 2019, 3: po.18.00335. PMID: 32914041, PMCID: PMC7450962, DOI: 10.1200/po.18.00335.Peer-Reviewed Original ResearchPD-1 signaling impacts T cell function during the early phase of infection with Toxoplasma gondii
Perry J, Delong J, Clark J, Park J, Gullicksrud J, Shallberg L, Konradt C, Christian D, Hunter C. PD-1 signaling impacts T cell function during the early phase of infection with Toxoplasma gondii. The Journal Of Immunology 2019, 202: 122.5-122.5. DOI: 10.4049/jimmunol.202.supp.122.5.Peer-Reviewed Original ResearchCD8+ T cellsPD-1 signalingPhase of infectionPD-1T cellsEarly phase of infectionPD-L1Inhibitory receptorsProportion of activated CD8+ T cellsExpression of multiple inhibitory receptorsPolyfunctional CD8+ T cellsCD8+ T cell responsesCD8+ T cell populationsTerminally differentiated T cellsExpression of inhibitory receptorsInfected CD8+ T cellsT cell effector differentiationProduction of IFN-gReduced parasite burdenIncreased immune pathologyMultiple inhibitory receptorsPD-L1 blockadeLigand PD-L1T cell responsesT cell populations
2017
Nivolumab combined with hypofractionated stereotactic irradiation (HFSRT) for patients with recurrent high grade gliomas: A phase I trial (NCT02829931).
Sahebjam S, Forsyth P, Arrington J, Tran N, Jaglal M, Mokhtari S, Long W, Macaulay R, Wicklund M, Drury-Sibiga A, Gatewood T, Robinson T, Raval R, Yu M. Nivolumab combined with hypofractionated stereotactic irradiation (HFSRT) for patients with recurrent high grade gliomas: A phase I trial (NCT02829931). Journal Of Clinical Oncology 2017, 35: tps2084-tps2084. DOI: 10.1200/jco.2017.35.15_suppl.tps2084.Peer-Reviewed Original ResearchHigh-grade gliomasPhase I trialGrade gliomasI trialPD-1PD-L1Grade IIIAnti-PD-1/PD-L1 blockadePD-1/PD-L1 blockadeRecurrent high-grade gliomaOngoing phase I trialDose-expansion cohortsPD-L1 blockadePrior radiation therapyTolerability of nivolumabGroup of patientsImmune checkpoint pathwaysLimited treatment optionsPreliminary antitumor activityOrthotopic murine modelLong-term survivalPrimary study objectiveIgG4 monoclonal antibodyNivolumab monotherapySafety cohort
2015
Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens
Baine MK, Turcu G, Zito CR, Adeniran AJ, Camp RL, Chen L, Kluger HM, Jilaveanu LB. Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens. Oncotarget 2015, 6: 24990-25002. PMID: 26317902, PMCID: PMC4694809, DOI: 10.18632/oncotarget.4572.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedB7-H1 AntigenCarcinoma, Renal CellCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesFemaleFluorescent Antibody TechniqueForkhead Transcription FactorsHumansKidney NeoplasmsLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasm MetastasisTissue Array AnalysisYoung AdultConceptsRenal cell carcinomaT cell ratioMetastatic specimensPD-L1Cell carcinomaPD-1/PD-L1 blockadePD-1/PD-L1 statusPD-1/PD-L1 pathwayMetastatic renal cell carcinomaHigh PD-L1PD-L1 blockadeUnfavorable tumor characteristicsPD-L1 expressionPD-L1 statusPD-L1 pathwayT-cell contentPre-treatment tumorsLow CD8TIL subsetsCharacterization of tumorsTIL densitySuch patientsTumor characteristicsImmune activationPatient survivalPD-1/PD-L1 Blockade Together With Vaccine Therapy Facilitates Effector T-Cell Infiltration Into Pancreatic Tumors
Soares KC, Rucki AA, Wu AA, Olino K, Xiao Q, Chai Y, Wamwea A, Bigelow E, Lutz E, Liu L, Yao S, Anders RA, Laheru D, Wolfgang CL, Edil BH, Schulick RD, Jaffee EM, Zheng L. PD-1/PD-L1 Blockade Together With Vaccine Therapy Facilitates Effector T-Cell Infiltration Into Pancreatic Tumors. Journal Of Immunotherapy 2015, 38: 1-11. PMID: 25415283, PMCID: PMC4258151, DOI: 10.1097/cji.0000000000000062.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaPD-1 blockadeT cellsObjective responsePD-L1PDA patientsPD-1/PD-L1 blockadePD-1/PD-L1 pathwayCytotoxic T-lymphocyte antigen-4Effector T-cell infiltrationPD-1 antibody monotherapyPD-L1 antibody therapySingle-agent checkpoint inhibitorsT-lymphocyte antigen-4Tumor microenvironmentMurine pancreatic ductal adenocarcinomaAddition of vaccineCTLA-4 pathwayImmune suppressive cellsImmune-suppressive signalsPD-L1 blockadePDA tumor microenvironmentLow-dose cyclophosphamideCD8 T lymphocytesPD-1 antibody
2014
1322P Biomarkers Associated with Clinical Activity of Pd-L1 Blockade in Non-Small Cell Lung Cancer (Nsclc) Patients (Pts) in a Phase I Study of Mpdl3280A
Soria J, Gettinger S, Gordon M, Heist R, Horn L, Spigel D, Kowanetz M, Mokatrin A, Xiao Y, Sandler A, Felip E. 1322P Biomarkers Associated with Clinical Activity of Pd-L1 Blockade in Non-Small Cell Lung Cancer (Nsclc) Patients (Pts) in a Phase I Study of Mpdl3280A. Annals Of Oncology 2014, 25: iv465. DOI: 10.1093/annonc/mdu349.101.Peer-Reviewed Original ResearchPD-L1 expressionPD-L1 blockadeIHC 2PD-L1Immune cellsNSCLC ptsB7-H4B7-H3PD-L2Tumor cellsIHC 0Clinical activityNon-small cell lung cancer patientsTumor-infiltrating immune cellsCell lung cancer patientsEmployees of GenentechReceptor PD-1Tumor immune microenvironmentLung cancer patientsPD-L1 IHCPD-L1 bindingRoche/GenentechImmune-related genesBristol-Myers SquibbPFS ratesBlockade of the B7-H1/PD-1 Pathway as a Basis for Combination Anticancer Therapy
Sznol M. Blockade of the B7-H1/PD-1 Pathway as a Basis for Combination Anticancer Therapy. The Cancer Journal 2014, 20: 290-295. PMID: 25098290, DOI: 10.1097/ppo.0000000000000056.Peer-Reviewed Original ResearchConceptsPD-1/PD-L1 blockadePD-L1 blockadeT cell responsesTumor-specific T-cell responsesB7-H1/PDCell responsesOverall risk-benefit ratioAntitumor T-cell responsesTumor microenvironmentAnimal tumor model systemsAbundant preclinical dataAutoimmune-like toxicitiesSubset of patientsRecent clinical trialsRisk-benefit ratioT lymphocyte suppressionEarly clinical developmentActivated T lymphocytesTumor model systemsCombination anticancer therapyClinical responseDurable responsesDeath-1Metastatic melanomaPreclinical data
2013
Biomarkers and associations with the clinical activity of PD-L1 blockade in a MPDL3280A study.
Powderly J, Koeppen H, Hodi F, Sosman J, Gettinger S, Desai R, Tabernero J, Soria J, Hamid O, Fine G, Xiao Y, Mokatrin A, Wu J, Anderson M, Irving B, Chen D, Kowanetz M. Biomarkers and associations with the clinical activity of PD-L1 blockade in a MPDL3280A study. Journal Of Clinical Oncology 2013, 31: 3001-3001. DOI: 10.1200/jco.2013.31.15_suppl.3001.Peer-Reviewed Original ResearchPD-L1 expressionPD-L1Blood-based biomarkersPD-1T cellsPD-L1 tumor expressionTumor samplesT-cell gene signaturePD-L1 blockadeT cell infiltrationMetastatic solid tumorsPD-L1 upregulationT cell reactivationT cell subsetsImmune cell subsetsTumor immune microenvironmentPretreatment tumor samplesAvailable tumor tissueHuman monoclonal antibodyActivated T cellsT cell activationTumor CD8Expansion cohortAntitumor immunityBiopsy cohort
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