2024
Development of anex vivo patient-derived tumor model (PDTM) to assess the tumor microenvironment in renal cell carcinoma (RCC)
Kashima S, Gupta R, Moritz V, Sadak K, Adeniran A, Humphrey P, Dinulescu D, Palmer D, Hammond S, Bosenberg M, Hurwitz M, Kenney P, Braun D. Development of anex vivo patient-derived tumor model (PDTM) to assess the tumor microenvironment in renal cell carcinoma (RCC). The Oncologist 2024, 29: s5-s6. PMCID: PMC11301923, DOI: 10.1093/oncolo/oyae181.008.Peer-Reviewed Original ResearchRCC tumor microenvironmentPatient-derived tumor modelsRenal cell carcinomaImmune checkpoint inhibitorsT cell functionPeripheral blood mononuclear cellsEnzyme-linked immunosorbent assayTumor microenvironmentT cellsFlow cytometryTumor fragmentsIFN-gTumor modelTumor samplesCytokine productionHealthy donor peripheral blood mononuclear cellsImpact of immune checkpoint inhibitorsAnti-PD-1 monoclonal antibodyDonor peripheral blood mononuclear cellsCD4+CD25+ regulatory T cellsCD8+ T cell populationsResection of renal cell carcinomaSurgical resection of renal cell carcinomaAnti-PD-1 antibodyMetastatic renal cell carcinoma22 Association of a germline single nucleotide polymorphism (SNP) in the interleukin-7 (IL7) gene with immune-related adverse events (irAEs)
Saad E, Mehrabad E, Labaki C, Saliby R, Semaan K, Eid M, Machaalani M, Chehade R, Nawfal R, Sun M, Sharon E, Shah P, Vemula S, Gupta S, Braun D, Van Allen E, Gusev A, Choueiri T. 22 Association of a germline single nucleotide polymorphism (SNP) in the interleukin-7 (IL7) gene with immune-related adverse events (irAEs). The Oncologist 2024, 29: s1-s2. PMCID: PMC11301885, DOI: 10.1093/oncolo/oyae181.003.Peer-Reviewed Original ResearchImmune-related adverse eventsMetastatic non-small cell lung cancerMetastatic renal cell carcinomaImmune checkpoint inhibitorsProgression-free survivalWhole-exome sequencingRecurrent grade 2Overall survivalGrade 2Interleukin-7Single nucleotide polymorphismsNivolumab armPembrolizumab armSomatic alterationsAdverse eventsTreatment armsPrediction of immune-related adverse eventsCumulative rates of adverse eventsTumor whole-exome sequencingRates of grade 2Non-small cell lung cancerGermline single nucleotide polymorphismsClinical trials of patientsAssociated with significantly higher ratesPD-1 inhibitorsExpression of the receptor tyrosine kinase AXL and clinical outcomes to cabozantinib and everolimus in patients with metastatic renal cell carcinoma enrolled in the METEOR trial.
Nabil Laimon Y, Paul M, Ghandour F, El Ahmar N, Matar S, Denize T, Bagheri Sheshdeh A, Savla V, Mohanna R, Sun M, Saliby R, Saad E, Machaalani M, Braun D, Aftab D, Xie W, CHOUEIRI T, Signoretti S. Expression of the receptor tyrosine kinase AXL and clinical outcomes to cabozantinib and everolimus in patients with metastatic renal cell carcinoma enrolled in the METEOR trial. Journal Of Clinical Oncology 2024, 42: 4543-4543. DOI: 10.1200/jco.2024.42.16_suppl.4543.Peer-Reviewed Original ResearchProgression-free survivalAssociated with progression-free survivalReceptor tyrosine kinase AXLTyrosine kinase inhibitorsRenal cell carcinomaImmune cellsMETEOR trialTyrosine kinase AXLAxl expressionTumor cellsCell carcinomaAssociated with shorter progression-free survivalMetastatic clear cell renal cell carcinomaAnti-PD-1 therapyLevels of AXL expressionMetastatic renal cell carcinomaMultitargeted tyrosine kinase inhibitorPresence of bone metastasesShorter progression-free survivalClear cell renal cell carcinomaIMDC risk groupsPretreatment tumor tissueVEGFR-TKI treatmentCell renal cell carcinomaDouble immunohistochemistry stainingMulti-omic characterization of acquired resistance to immune checkpoint inhibitors in patients with metastatic renal cell carcinoma.
Saad E, Labaki C, Miron B, Park J, Bakouny Z, Nassar A, Saliby R, Semaan K, Eid M, Meli K, Nabil Laimon Y, Geynisman D, Kokate R, Braun D, Signoretti S, McGregor B, Plimack E, Choueiri T, Van Allen E, Zibelman M. Multi-omic characterization of acquired resistance to immune checkpoint inhibitors in patients with metastatic renal cell carcinoma. Journal Of Clinical Oncology 2024, 42: 459-459. DOI: 10.1200/jco.2024.42.4_suppl.459.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaImmune checkpoint inhibitorsTertiary lymphoid structuresWhole-exome sequencingDifferential gene expression analysisRenal cell carcinomaGene set enrichment analysisCheckpoint inhibitorsCell carcinomaB cellsAbsence of tertiary lymphoid structuresGene mutationsResistance to immune checkpoint inhibitorsPresence of tertiary lymphoid structuresImmune checkpoint inhibitor treatmentRNA-seqInitial response to therapyCD8+ T cell fractionCohort of ptsICI-based regimensDana-Farber Cancer InstituteT cell functionResponse to therapyNaive B cellsT-cell fractionEvaluating intermediate endpoints (IE) for overall survival (OS) in metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICI): An IMDC study.
Saliby R, Xie W, Wells J, Saad E, Eid M, Labaki C, Semaan K, Ferrier E, Lemelin A, Suárez C, Ruiz-Morales J, Powles T, Wood L, Ebrahimi H, de Velasco G, Takemura K, Agarwal N, Braun D, Heng D, Choueiri T. Evaluating intermediate endpoints (IE) for overall survival (OS) in metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICI): An IMDC study. Journal Of Clinical Oncology 2024, 42: 400-400. DOI: 10.1200/jco.2024.42.4_suppl.400.Peer-Reviewed Original ResearchTime to next therapyTime to treatment failureInternational mRCC Database ConsortiumImmune checkpoint inhibitorsMetastatic renal cell carcinomaOverall survivalIntermediate endpointsHazard ratioInternational mRCC Database Consortium risk groupTreated with immune checkpoint inhibitorsDual immune checkpoint inhibitorsICI startICI-based regimensAssociated with OSAssociation of OSEndpoint of OSRenal cell carcinomaCheckpoint inhibitorsNext therapyMetastatic sitesDrug cessationTreatment failurePrimary endpointCell carcinomaMedian ageUpdate on Biomarkers in Renal Cell Carcinoma.
Saliby R, Saad E, Kashima S, Schoenfeld D, Braun D. Update on Biomarkers in Renal Cell Carcinoma. American Society Of Clinical Oncology Educational Book 2024, 44: e430734. PMID: 38207251, DOI: 10.1200/edbk_430734.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRenal cell carcinomaCell carcinomaMetastatic renal cell carcinomaTumor intrinsic featuresImmune checkpoint inhibitorsRobust predictive biomarkersCheckpoint inhibitorsDurable responsesOverall survivalCare regimensPathological characteristicsPredictive biomarkersTherapeutic responseTreatment paradigmImmune systemHost factorsTranscriptional signatureGenomic alterationsTumor heterogeneityBiomarkersCarcinomaBiomarker discoveryInnovative technological approachesRegimens
2023
Novel Immune Therapies for Renal Cell Carcinoma Looking Beyond the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte-Associated Protein 4 Axes
Saad E, Saliby R, Labaki C, Xu W, Viswanathan S, Braun D, Bakouny Z. Novel Immune Therapies for Renal Cell Carcinoma Looking Beyond the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte-Associated Protein 4 Axes. Hematology/Oncology Clinics Of North America 2023, 37: 1027-1040. PMID: 37391289, DOI: 10.1016/j.hoc.2023.05.023.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRenal cell carcinomaCell carcinomaMetastatic renal cell carcinomaCell death protein 1Programmed Cell Death Protein 1Novel immune targetsDeath protein 1Novel immune therapiesNovel immunotherapiesImmune therapyClinical evidenceImmune targetsImmune systemInhibitory stimuliTumoral cellsProtein 1ImmunotherapyPatientsCarcinomaImmunosuppressionTherapy
2019
State of the Future: Translational Approaches in Renal Cell Carcinoma in the Immunotherapy Era
Bakouny Z, Flippot R, Braun D, Lalani A, Choueiri T. State of the Future: Translational Approaches in Renal Cell Carcinoma in the Immunotherapy Era. European Urology Focus 2019, 6: 37-40. PMID: 30827939, DOI: 10.1016/j.euf.2019.02.014.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaCell carcinomaImmune systemTherapeutic resistanceMetastatic renal cell carcinomaImmune checkpoint inhibitorsMetastatic kidney cancerSubset of patientsPatient's immune systemImmunotherapy eraCheckpoint inhibitorsTreatment optionsKidney cancerPatientsTranslational approachTranslational researchImaging modalitiesCarcinomaTherapyTumorsNovel technological advancesSubstantial numberBiomarker discoveryBrief reportTumor spheroids