2024
Synergistic Immunoregulation: harnessing CircRNAs and PiRNAs to Amplify PD-1/PD-L1 Inhibition Therapy
Han R, Rao X, Zhou H, Lu L. Synergistic Immunoregulation: harnessing CircRNAs and PiRNAs to Amplify PD-1/PD-L1 Inhibition Therapy. International Journal Of Nanomedicine 2024, 19: 4803-4834. PMID: 38828205, PMCID: PMC11144010, DOI: 10.2147/ijn.s461289.Peer-Reviewed Original ResearchConceptsRegulate PD-L1 expressionPD-L1 expressionPD-1/PD-L1Inhibition therapySensitive to immune checkpoint inhibitorsEfficacy of cancer immunotherapyPD-1/PD-L1 inhibitorsImmune checkpoint inhibitorsAnti-cancer immunityEfficacy of monotherapyExploration of combination strategiesModulate immune responsesMRNA vaccine technologyCheckpoint inhibitorsCancer immunotherapyRNA-based therapiesTreatment strategiesImmunomodulatory effectsCancer therapyImmune responseTherapyCancer treatmentVaccine technologyCombination strategiesCancer
2023
Dynamic changes of circulating soluble PD-1/PD-L1 and its association with patient survival in immune checkpoint blockade-treated melanoma
Lu L, Risch E, Halaban R, Zhen P, Bacchiocchi A, Risch H. Dynamic changes of circulating soluble PD-1/PD-L1 and its association with patient survival in immune checkpoint blockade-treated melanoma. International Immunopharmacology 2023, 118: 110092. PMID: 37004344, DOI: 10.1016/j.intimp.2023.110092.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeSoluble PD-L1 (sPD-L1) levelsPD-L1 ratioPD-L1 levelsSoluble PD-1Soluble PD-L1PD-L1PD-1Patient survivalSurvival statusPD-1/PD-L1Immune checkpoints PD-1T cell exhaustionPatients' survival statusSolid tumor typesInitial immunotherapyCheckpoint blockadeMelanoma patientsPoor prognosisRetrospective studyPatient responseCell exhaustionTumor typesMelanomaSurvival
2022
Location matters: LAG3 levels are lower in renal cell carcinoma metastatic sites compared to primary tumors, and expression at metastatic sites only may have prognostic importance
Schoenfeld D, Merkin R, Moutafi M, Martinez S, Adeniran A, Kumar D, Jilaveanu L, Hurwitz M, Rimm D, Kluger H. Location matters: LAG3 levels are lower in renal cell carcinoma metastatic sites compared to primary tumors, and expression at metastatic sites only may have prognostic importance. Frontiers In Oncology 2022, 12: 990367. PMID: 36313654, PMCID: PMC9608089, DOI: 10.3389/fonc.2022.990367.Peer-Reviewed Original ResearchRenal cell carcinomaImmune checkpoint inhibitorsMetastatic sitesBrain metastasesPrimary tumorMechanisms of resistancePD-1/PD-L1Anti-PD-1 therapyHigh-risk clinical characteristicsLarger primary tumor sizeAdvanced renal cell carcinomaAlternative immune checkpointsCertain drug regimensPoor-risk diseasePD-1 inhibitorsMinority of patientsPrimary tumor sizeLonger overall survivalGrade 4 tumorsProtein levelsPrimary RCC tumorsAttractive therapeutic targetIdentification of subgroupsCheckpoint inhibitorsUpfront therapyAssociation of PD-1/PD-L1 Co-location with Immunotherapy Outcomes in Non-Small Cell Lung Cancer
Gavrielatou N, Liu Y, Vathiotis I, Zugazagoitia J, Aung TN, Shafi S, Fernandez A, Schalper K, Psyrri A, Rimm DL. Association of PD-1/PD-L1 Co-location with Immunotherapy Outcomes in Non-Small Cell Lung Cancer. Clinical Cancer Research 2022, 28: clincanres.2649.2021. PMID: 34686497, PMCID: PMC8776595, DOI: 10.1158/1078-0432.ccr-21-2649.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerBest overall responsePD-L1 tumor proportion scorePD-1/PD-L1Immune checkpoint inhibitorsProgression-free survivalTumor proportion scoreCell lung cancerPD-L1Immunotherapy outcomesCheckpoint inhibitorsOverall survivalQuantitative immunofluorescenceLung cancerProportion scoreAdvanced non-small cell lung cancerLocal T cell responsesCell death protein 1Immunotherapy-treated patientsMultiplexed quantitative immunofluorescencePD-1 expressionPD-L1 expressionDeath protein 1Selection of patientsT cell responses
2021
Minimal Toxicity Seen When Pembrolizumab Is Added to Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia and Persistently Detectable Minimal Residual Disease: Early Results from an Ongoing Phase II Trial (ECOG-ACRIN EA9171)
Zeidan A, Roopcharan K, Radich J, Bewersdorf J, Bhatt V, Sharon E, Little R, Gore S, Caldwell A, Luger S, Litzow M. Minimal Toxicity Seen When Pembrolizumab Is Added to Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia and Persistently Detectable Minimal Residual Disease: Early Results from an Ongoing Phase II Trial (ECOG-ACRIN EA9171). Blood 2021, 138: 3613. DOI: 10.1182/blood-2021-145015.Peer-Reviewed Original ResearchUndetectable minimal residual diseaseClinical Trials CommitteeTherapy-free remissionCombination of TKIG3 adverse eventsImmune-related AEAdverse eventsTrials CommitteeMinimal residual diseaseSafety cohortTKI discontinuationTKI therapyPD-L1Residual diseasePilot phase II clinical trialPD-1/PD-L1Detectable minimal residual diseaseImmune-related adverse eventsNon-hematologic adverse eventsAnti-PD-1 antibodyOngoing phase II trialBCR-ABLPhase II clinical trialAdvisory CommitteeDaiichi Sankyo
2020
Blast MRD CML 1 Trial: Blockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease (MRD) in Chronic Myeloid Leukemia (CML)- a Phase II Study of Adding the Anti-PD-1 Pembrolizumab to Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia and Persistently Detectable Minimal Residual Disease: A Trial of the ECOG-ACRIN Cancer Research Group (EA9171)
Zeidan A, Wang V, Radich J, Bewersdorf J, Bhatt V, Sharon E, Gore S, Luger S, Litzow M. Blast MRD CML 1 Trial: Blockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease (MRD) in Chronic Myeloid Leukemia (CML)- a Phase II Study of Adding the Anti-PD-1 Pembrolizumab to Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia and Persistently Detectable Minimal Residual Disease: A Trial of the ECOG-ACRIN Cancer Research Group (EA9171). Blood 2020, 136: 1. DOI: 10.1182/blood-2020-137734.Peer-Reviewed Original ResearchUndetectable minimal residual diseaseChronic myeloid leukemiaMeasurable residual diseaseTyrosine kinase inhibitorsTKI discontinuationTKI therapyMinimal residual diseaseCML patientsResidual diseaseMyeloid leukemiaBristol-Myers SquibbPembrolizumab therapyAdverse eventsPD-1T cellsCML cellsAnti-PD-1/PD-L1 therapyBlast phase chronic myeloid leukemiaPilot phase II clinical trialThird-line tyrosine kinase inhibitorsAllogeneic hematopoietic stem cell transplantAnti-PD-1 monoclonal antibodyPD-1/PD-L1Anti-PD-1 pembrolizumabDetectable minimal residual diseaseImmune checkpoint inhibition in myeloid malignancies: Moving beyond the PD-1/PD-L1 and CTLA-4 pathways
Bewersdorf JP, Shallis RM, Zeidan AM. Immune checkpoint inhibition in myeloid malignancies: Moving beyond the PD-1/PD-L1 and CTLA-4 pathways. Blood Reviews 2020, 45: 100709. PMID: 32487480, DOI: 10.1016/j.blre.2020.100709.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmune checkpoint inhibitorsMyeloid malignanciesPD-1/PD-L1CTLA-4 pathwayImmune checkpoint inhibitionAcute myeloid leukemiaSafe combination therapyICI therapyImmunologic landscapeCheckpoint inhibitorsDisease coursePD-L1Checkpoint inhibitionMyelodysplastic syndromeCombination therapyMechanisms of resistanceClinical trialsMyeloid leukemiaClinical developmentPotential biomarkersNovel targetPatientsMalignancyTherapyBiomarkersSafety and clinical activity of atezolizumab (atezo) + radium-223 dichloride (r-223) in 2L metastatic castration-resistant prostate cancer (mCRPC): Results from a phase Ib clinical trial.
Morris M, Fong L, Petrylak D, Sartor A, Higano C, Pagliaro L, Alva A, Appleman L, Tan W, Vaishampayan U, Porcu R, Tayama D, Kadel E, Yuen K, Datye A, Armstrong A. Safety and clinical activity of atezolizumab (atezo) + radium-223 dichloride (r-223) in 2L metastatic castration-resistant prostate cancer (mCRPC): Results from a phase Ib clinical trial. Journal Of Clinical Oncology 2020, 38: 5565-5565. DOI: 10.1200/jco.2020.38.15_suppl.5565.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerPSA response ratePSA progressionDosing schedulesPD-L1Clinical benefitResponse ratePD-1/PD-L1Castration-resistant prostate cancerPhase Ib clinical trialPhase 1b studyPhase Ib studyTumor-directed radiationAnti-tumor immunityDose-limiting toxicityRadium-223 dichlorideLimited treatment optionsMechanism of actionEvaluable ptsRadiographic PFSMCRPC patientsMedian OSBaseline characteristicsEvaluable dataUnacceptable toxicityThe path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers in breast cancer clinical trials and daily practice
Gonzalez‐Ericsson P, Stovgaard ES, Sua LF, Reisenbichler E, Kos Z, Carter JM, Michiels S, Le Quesne J, Nielsen TO, Lænkholm A, Fox SB, Adam J, Bartlett JM, Rimm DL, Quinn C, Peeters D, Dieci MV, Vincent‐Salomon A, Cree I, Hida AI, Balko JM, Haynes HR, Frahm I, Acosta‐Haab G, Balancin M, Bellolio E, Yang W, Kirtani P, Sugie T, Ehinger A, Castaneda CA, Kok M, McArthur H, Siziopikou K, Badve S, Fineberg S, Gown A, Viale G, Schnitt SJ, Pruneri G, Penault‐Llorca F, Hewitt S, Thompson EA, Allison KH, Symmans WF, Bellizzi AM, Brogi E, Moore DA, Larsimont D, Dillon DA, Lazar A, Lien H, Goetz MP, Broeckx G, Bairi K, Harbeck N, Cimino‐Mathews A, Sotiriou C, Adams S, Liu S, Loibl S, Chen I, Lakhani SR, Juco JW, Denkert C, Blackley EF, Demaria S, Leon‐Ferre R, Gluz O, Zardavas D, Emancipator K, Ely S, Loi S, Salgado R, Sanders M, Group I. The path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers in breast cancer clinical trials and daily practice. The Journal Of Pathology 2020, 250: 667-684. PMID: 32129476, DOI: 10.1002/path.5406.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerTumor-infiltrating lymphocytesPD-L1Breast cancerPatient selectionInter-reader reproducibilityEarly-stage triple-negative breast cancerPD-1/PD-L1 inhibitorsStage triple-negative breast cancerAdvanced triple-negative breast cancerPD-1/PD-L1High tumor-infiltrating lymphocytesImmune checkpoint inhibitor therapyAddition of atezolizumabPD-L1 assessmentSuboptimal patient selectionCheckpoint inhibitor therapyOptimal patient selectionPD-L1 expressionPD-L1 inhibitorsDaily practiceStandard of careImmuno-therapeutic approachesNegative breast cancerEosin-stained slidesDifferential expression of the T-cell inhibitor TIGIT in glioblastoma and MS
Lucca LE, Lerner BA, Park C, DeBartolo D, Harnett B, Kumar VP, Ponath G, Raddassi K, Huttner A, Hafler DA, Pitt D. Differential expression of the T-cell inhibitor TIGIT in glioblastoma and MS. Neurology Neuroimmunology & Neuroinflammation 2020, 7: e712. PMID: 32269065, PMCID: PMC7188477, DOI: 10.1212/nxi.0000000000000712.Peer-Reviewed Original ResearchConceptsTumor-infiltrating T cellsT cellsPD-1/PD-L1Anti-TIGIT therapyExpression of CD226Expression of TIGITPostmortem CNS tissueLymphocytes of patientsFresh surgical resectionsLigand CD155TIGIT expressionSurgical resectionPD-1PD-L1CNS diseaseHealthy controlsHealthy donorsLymphocytic expressionImmune responseCNS tissueMS lesionsTIGITImmune pathwaysPatientsGlioblastoma multiformeAdenosine 2A Receptor Blockade as an Immunotherapy for Treatment-Refractory Renal Cell Cancer
Fong L, Hotson A, Powderly JD, Sznol M, Heist RS, Choueiri TK, George S, Hughes BGM, Hellmann MD, Shepard DR, Rini BI, Kummar S, Weise AM, Riese MJ, Markman B, Emens LA, Mahadevan D, Luke JJ, Laport G, Brody JD, Hernandez-Aya L, Bonomi P, Goldman JW, Berim L, Renouf DJ, Goodwin RA, Munneke B, Ho PY, Hsieh J, McCaffery I, Kwei L, Willingham SB, Miller RA. Adenosine 2A Receptor Blockade as an Immunotherapy for Treatment-Refractory Renal Cell Cancer. Cancer Discovery 2020, 10: 40-53. PMID: 31732494, PMCID: PMC6954326, DOI: 10.1158/2159-8290.cd-19-0980.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Renal CellDrug Resistance, NeoplasmFemaleFollow-Up StudiesFuransHumansKidney NeoplasmsMaleMiddle AgedNeoplasm Recurrence, LocalPrognosisPyridinesPyrimidinesReceptor, Adenosine A2ASalvage TherapySurvival RateConceptsRenal cell cancerPretreatment tumor biopsiesClinical responseGene expression signaturesCell cancerTumor biopsiesPD-1/PD-L1 inhibitorsPD-1/PD-L1Refractory renal cell cancerPhase I clinical trialL1 combination therapyRecruitment of CD8Targetable immune checkpointsDurable clinical benefitPD-L1 inhibitorsT cell repertoireAdenosine 2A receptorAntitumor immunityReceptor blockadeImmune checkpointsPD-L1L1 antibodyClinical benefitCombination therapyImmune cells
2019
RBTT-07. A PHASE 2 TRIAL OF PEMBROLIZUMAB AND BEVACIZUMAB IN MELANOMA BRAIN MET PATIENTS
Kluger H, Forsyth P, Khushalani N, Eroglu Z, Sznol M, Tran T, Jilaveanu L, Cohen J, Hegde U, Wei W, Mahajan A, Goldberg S, Chiang V, Weiss S. RBTT-07. A PHASE 2 TRIAL OF PEMBROLIZUMAB AND BEVACIZUMAB IN MELANOMA BRAIN MET PATIENTS. Neuro-Oncology 2019, 21: vi220-vi220. PMCID: PMC6847787, DOI: 10.1093/neuonc/noz175.919.Peer-Reviewed Original ResearchVEGF inhibitorsPrimary endpointPD-1/PD-L1Anti-PD-1 activityGrade 3 ALT elevationPre-specified primary endpointPhase 2 studyPhase 2 trialUnconfirmed PRALT elevationDiverticular perforationMetS patientsCerebral edemaPD-L1Wound dehiscencePembroToxicity profileEdemaFurther studiesPromising activityEndpointBRAFmtPembrolizumabMucositisULNHyperprogressive Disease during Anti-PD-1 (PDCD1) / PD-L1 (CD274) Therapy: A Systematic Review and Meta-Analysis
Kim J, Lee K, Kang J, Borcoman E, Saada-Bouzid E, Kronbichler A, Hong S, de Rezende L, Ogino S, Keum N, Song M, Luchini C, van der Vliet H, Shin J, Gamerith G. Hyperprogressive Disease during Anti-PD-1 (PDCD1) / PD-L1 (CD274) Therapy: A Systematic Review and Meta-Analysis. Cancers 2019, 11: 1699. PMID: 31683809, PMCID: PMC6896059, DOI: 10.3390/cancers11111699.Peer-Reviewed Original ResearchHyperprogressive diseasePD-L1PD-1/PD-L1 inhibitor therapyRoyal Marsden Hospital prognostic scoreInitiation of immune checkpoint inhibitorsMeta-analysisAssociated with hyperprogressive diseaseDefinition of HPDIncidence of hyperprogressive diseasePD-L1 expression statusSmall-study effectsOdds ratioNon-small cell lung cancerSubset analysis of patientsAssociated with poor survivalAnti-PD-1Immune checkpoint inhibitorsPD-L1 expressionPD-1/PD-L1Baseline patient factorsRapid tumor progressionCell lung cancerUpper normal limitAnalysis of patientsSerum lactate dehydrogenaseFibroblast Growth Factor Receptor 3 Alterations and Response to PD-1/PD-L1 Blockade in Patients with Metastatic Urothelial Cancer
Wang L, Gong Y, Saci A, Szabo P, Martini A, Necchi A, Siefker-Radtke A, Pal S, Plimack E, Sfakianos J, Bhardwaj N, Horowitz A, Farkas A, Mulholland D, Fischer B, Oh W, Sharma P, Zhu J, Galsky M. Fibroblast Growth Factor Receptor 3 Alterations and Response to PD-1/PD-L1 Blockade in Patients with Metastatic Urothelial Cancer. European Urology 2019, 76: 599-603. PMID: 31272788, PMCID: PMC6801024, DOI: 10.1016/j.eururo.2019.06.025.Peer-Reviewed Original ResearchConceptsT cell infiltrationUrothelial cancerFGFR3 mutationsAssociated with decreased T-cell infiltrationFGFR3 alterationsResponse to PD-1/PD-L1 blockadeLow T-cell infiltrationPD-1/PD-L1 inhibitionPoor T-cell infiltrationPD-1/PD-L1 blockadeResponse rateMetastatic urothelial cancerSingle-agent activityPD-1/PD-L1Tumor mutational burdenNon-cross-resistantTumors harboring mutationsFGFR3 mutation statusHypothesis-generating dataSimilar to patientsResponse to treatmentBiomarkers of resistanceGrowth factor-betaStatistically significant differenceMetastatic UCProgrammed 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 inhibitionA first-in-human phase I study of FS118, an anti-LAG-3/PD-L1 bispecific antibody in patients with solid tumors that have progressed on prior PD-1/PD-L1 therapy.
Yap T, Papadopoulos K, LoRusso P, Wong D, Hu-Lieskovan S, Holz J. A first-in-human phase I study of FS118, an anti-LAG-3/PD-L1 bispecific antibody in patients with solid tumors that have progressed on prior PD-1/PD-L1 therapy. Journal Of Clinical Oncology 2019, 37: tps2652-tps2652. DOI: 10.1200/jco.2019.37.15_suppl.tps2652.Peer-Reviewed Original ResearchSafety Review CommitteePD-L1Dose escalationLAG-3PD-1/PD-L1 checkpoint inhibitorsPD-1/PD-L1 therapyPD-1/PD-L1 treatmentTranslational studiesSolid tumorsPD-1/PD-L1Immunotherapy-related adverse effectsPD-L1 checkpoint inhibitorsBispecific antibodiesLymphocyte activation gene-3PD-1 mAbPD-L1 treatmentPhase 2 dosePD-L1 therapyLAG-3 expressionMinority of patientsAnti-tumor responseSuperior anti-tumor efficacyEarly clinical trialsRemarkable anti-tumor activityHuman phase IExpression of PD-1 by T Cells in Malignant Glioma Patients Reflects Exhaustion and Activation
Davidson T, Lee A, Hsu M, Sedighim S, Orpilla J, Treger J, Mastall M, Roesch S, Rapp C, Galvez M, Mochizuki A, Antonios J, Garcia A, Kotecha N, Bayless N, Nathanson D, Wang A, Everson R, Yong W, Cloughesy T, Liau L, Herold-Mende C, Prins R. Expression of PD-1 by T Cells in Malignant Glioma Patients Reflects Exhaustion and Activation. Clinical Cancer Research 2019, 25: 1913-1922. PMID: 30498094, PMCID: PMC6420851, DOI: 10.1158/1078-0432.ccr-18-1176.Peer-Reviewed Original ResearchConceptsPD-1<sup>+</sup> T cellsTumor-infiltrating lymphocytesPD-1<sup>+</sup> tumor-infiltrating lymphocytesPD-1 expressionPD-1T cellsPD-1<sup>+</supMalignant gliomasT lymphocytesEffective antitumor T-cell responsesExpression of markers of activationAntitumor T-cell responsesPD-1 blocking therapyExpression of PD-1Peripheral blood T lymphocytesExpressed PD-1PD-1/PD-L1T cell responsesBlood T lymphocytesIncreased proliferative capacityMarkers of activationPrimary malignant tumorHuman T lymphocytesHallmarks of memoryCentral nervous systemEffect of concurrent beta-blocker (BB) use in patients receiving immune checkpoint inhibitors for metastatic urothelial (mUC) and renal cell carcinomas (mRCC).
Patel V, Oh W, Galsky M, Liaw B, Tsao C. Effect of concurrent beta-blocker (BB) use in patients receiving immune checkpoint inhibitors for metastatic urothelial (mUC) and renal cell carcinomas (mRCC). Journal Of Clinical Oncology 2019, 37: 467-467. DOI: 10.1200/jco.2019.37.7_suppl.467.Peer-Reviewed Original ResearchCheckpoint inhibitorsDuration of therapyNon-BB groupBeta-blockersOverall survivalBB groupCD8+ T cell activationEfficacy of checkpoint inhibitorsPD-1/PD-L1 blockadePre-clinical mouse modelImmune checkpoint inhibitorsPharmacological beta-blockadeCheckpoint inhibitor therapyPD-1/PD-L1IRB-approved databaseSingle-center cohortResponse of immunotherapyOutcomes of patientsMolecular targeted therapyRenal cell carcinomaKaplan-Meier curvesT cell activationCox proportional hazards modelsGU cancer patientsProportional hazards model
2018
Quantitative Spatial Profiling of PD-1/PD-L1 Interaction and HLA-DR/IDO-1 Predicts Improved Outcomes of Anti–PD-1 Therapies in Metastatic Melanoma
Johnson DB, Bordeaux J, Kim J, Vaupel C, Rimm DL, Ho TH, Joseph RW, Daud AI, Conry RM, Gaughan EM, Hernandez-Aya LF, Dimou A, Funchain P, Smithy J, Witte JS, McKee SB, Ko J, Wrangle J, Dabbas B, Tangri S, Lameh J, Hall J, Markowitz J, Balko JM, Dakappagari N. Quantitative Spatial Profiling of PD-1/PD-L1 Interaction and HLA-DR/IDO-1 Predicts Improved Outcomes of Anti–PD-1 Therapies in Metastatic Melanoma. Clinical Cancer Research 2018, 24: 5250-5260. PMID: 30021908, PMCID: PMC6214750, DOI: 10.1158/1078-0432.ccr-18-0309.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyCell Line, TumorFemaleHLA-DR AntigensHumansImmunohistochemistryIndoleamine-Pyrrole 2,3,-DioxygenaseMaleMelanomaMiddle AgedModels, BiologicalNeoplasm MetastasisNeoplasm StagingPrognosisProgrammed Cell Death 1 ReceptorProtein BindingRetreatmentTreatment OutcomeConceptsAnti-PD-1 responseHLA-DRValidation cohortPD-1/PD-L1PD-1 blockersPD-1 monotherapyPD-L1 expressionPretreatment tumor biopsiesProgression-free survivalSubset of patientsAcademic cancer centerBiomarkers of responseIndependent validation cohortClin Cancer ResImmunosuppression mechanismsClinical responseOverall survivalPD-L1Melanoma patientsCancer CenterTreatment outcomesTumor biopsiesDiscovery cohortPatientsIndividual biomarkersDocetaxel with or without ramucirumab after immune checkpoint inhibition in platinum-refractory metastatic urothelial carcinoma (mUC): Prespecified subgroup analysis from the phase 3 RANGE trial.
Drakaki A, Kirby C, Van Der Heijden M, Petrylak D, Powles T, Chi K, Flechon A, Necchi A, Geczi L, Lee J, Gakis G, Bracarda S, Chowdhury S, Lin C, Keizman D, Vaishampayan U, Liepa A, Zimmermann A, Bell-McGuinn K, Castellano D. Docetaxel with or without ramucirumab after immune checkpoint inhibition in platinum-refractory metastatic urothelial carcinoma (mUC): Prespecified subgroup analysis from the phase 3 RANGE trial. Journal Of Clinical Oncology 2018, 36: 434-434. DOI: 10.1200/jco.2018.36.6_suppl.434.Peer-Reviewed Original ResearchPlatinum-refractory metastatic urothelial carcinomaImmune checkpoint inhibitorsMetastatic urothelial carcinomaObjective response ratePrior immune checkpoint inhibitorsLiver metastasesPD-L1Subgroup analysisDouble-blinded phase 3 trialPD-1/PD-L1Disease sitesHigher objective response ratePre-specified subgroup analysisInvestigator-assessed PFSImmune checkpoint inhibitionProgression-free survivalPhase 3 trialPrespecified subgroup analysisPlatinum-based chemotherapyFrequency of gradeICI therapyMedian PFSSecondary endpointsCheckpoint inhibitorsData cutoff
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