2024
Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma
Schoenfeld D, Djureinovic D, Su D, Zhang L, Lu B, Kamga L, Mann J, Huck J, Hurwitz M, Braun D, Jilaveanu L, Ring A, Kluger H. Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma. JCI Insight 2024 PMID: 39561007, DOI: 10.1172/jci.insight.184545.Peer-Reviewed Original ResearchAnti-CTLA-4Renal cell carcinomaIL-18IL-18BPCell carcinomaTumor microenvironmentTumor typesPatients treated with immune checkpoint inhibitorsRegulatory T cell levelsAnti-PD-1 treatmentCD8+ T cellsAnti-PD-1Immune checkpoint inhibitorsCell renal cell carcinomaNon-responder patientsMyeloid cell populationsT cell levelsCytokine interleukin-18Anti-cancer efficacySecreted binding proteinCheckpoint inhibitorsResponding patientsPreclinical modelsT cellsMurine model1705P Association between baseline radiological tumor burden (BRTB) and outcomes in metastatic clear cell renal cell carcinoma (mccRCC) treated with first line (1L) immunotherapy (IO)-based regimens
Nawfal R, Semaan K, Eid M, Paul M, Saliby R, Chehade R, Machaalani M, Saad E, Phillips N, Canniff J, Vasseur D, Zarif T, Yekeduz E, Sun M, Baca S, Braun D, Xie W, Krajewski K, Choueiri T. 1705P Association between baseline radiological tumor burden (BRTB) and outcomes in metastatic clear cell renal cell carcinoma (mccRCC) treated with first line (1L) immunotherapy (IO)-based regimens. Annals Of Oncology 2024, 35: s1022-s1023. DOI: 10.1016/j.annonc.2024.08.1798.Peer-Reviewed Original Research1702P Updated results of phase II study of cabozantinib (Cabo) with nivolumab (Nivo) and ipilimumab (Ipi) in advanced renal cell carcinoma with divergent histologies (RCCdh)
McGregor B, Paul M, Xie W, Xu W, Bilen M, Braun D, Berg S, Zhang T, McKay R, McDermott D, Hammers H, Choueiri T. 1702P Updated results of phase II study of cabozantinib (Cabo) with nivolumab (Nivo) and ipilimumab (Ipi) in advanced renal cell carcinoma with divergent histologies (RCCdh). Annals Of Oncology 2024, 35: s1020. DOI: 10.1016/j.annonc.2024.08.1795.Peer-Reviewed Original Research1704P Potential surrogate endpoints for overall survival (OS) in immunotherapy (IO)-treated metastatic renal cell carcinoma (mRCC): An International Metastatic Database Consortium (IMDC) study
Saliby R, Xie W, Wells J, Saad E, Eid M, Semaan K, Labaki C, Ferrier E, Zarba M, Ebrahimi H, Rodriguez C, Ruiz J, Powles T, Wood L, De Velasco Oria G, Takemura K, Braun D, Heng D, Choueiri T. 1704P Potential surrogate endpoints for overall survival (OS) in immunotherapy (IO)-treated metastatic renal cell carcinoma (mRCC): An International Metastatic Database Consortium (IMDC) study. Annals Of Oncology 2024, 35: s1021-s1022. DOI: 10.1016/j.annonc.2024.08.1797.Peer-Reviewed Original ResearchFirst-line Systemic Therapy Following Adjuvant Immunotherapy in Renal Cell Carcinoma: An International Multicenter Study
El Zarif T, Semaan K, Xie W, Eid M, Zarba M, Issa W, Zhang T, Nguyen C, Alva A, Fahey C, Beckermann K, Karam J, Campbell M, Procopio G, Stellato M, Buti S, Zemankova A, Melichar B, Massari F, Mollica V, Venugopal B, Ebrahimi H, de Velasco G, Gurney H, De Giorgi U, Parikh O, Winquist E, Master V, Garcia A, Cutuli H, Ferguson T, Gross-Goupil M, Baca S, Pal S, Braun D, McKay R, Heng D, Choueiri T. First-line Systemic Therapy Following Adjuvant Immunotherapy in Renal Cell Carcinoma: An International Multicenter Study. European Urology 2024 PMID: 39147674, DOI: 10.1016/j.eururo.2024.07.016.Peer-Reviewed Original ResearchRenal cell carcinomaProgression-free survivalInternational Metastatic RCC Database ConsortiumRecurrent renal cell carcinomaTreatment-related adverse eventsSystemic therapyAdjuvant pembrolizumabOverall survivalCell carcinomaClinical outcomesIO therapyAdjuvant immunotherapyAdverse eventsVascular endothelial growth factor-targeted therapyDetect occult metastatic diseaseOutcomes of first-lineFirst-line systemic therapyFavorable-risk diseaseIO-based regimensOccult metastatic diseaseMedian follow-upKaplan-Meier methodShort follow-up periodFollow-up periodInternational multicenter studyTIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3
Perales O, Jilaveanu L, Adeniran A, Su D, Hurwitz M, Braun D, Kluger H, Schoenfeld D. TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3. Cancer Immunology, Immunotherapy 2024, 73: 192. PMID: 39105820, PMCID: PMC11303630, DOI: 10.1007/s00262-024-03773-8.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaRenal cell carcinoma tumorsT cellsTIGIT expressionCheckpoint inhibitorsPD-1Likelihood of response to therapyTumor-infiltrating T cellsCD3+ T cellsRenal cell carcinoma metastasisTreatment of renal cell carcinomaImmune checkpoint inhibitorsInfiltrating T cellsPurposeImmune checkpoint inhibitorsResponse to therapyT cell immunoglobulinCD3+ levelsMetastatic RCC specimensAdjacent normal renal tissuesNormal renal tissuesQuantitative immunofluorescence analysisCell carcinomaResistant diseasePotential therapeutic targetTissue microarray14 Natural killer cells have impaired cytotoxicity in advanced renal cell carcinoma
Moritz V, Xu W, Birch G, Meliki A, Bharadwaj M, Schindler N, Labaki C, Saliby R, Dinh K, Horst J, Sun M, Kashima S, Machaalani M, Lee G, Hurwitz M, McGregor B, Hirsch M, Shukla S, McDermott D, Signoretti S, Romee R, Choueiri T, Braun D. 14 Natural killer cells have impaired cytotoxicity in advanced renal cell carcinoma. The Oncologist 2024, 29: s7-s8. PMCID: PMC11301877, DOI: 10.1093/oncolo/oyae181.012.Peer-Reviewed Original ResearchNK cell phenotypeGene expression signaturesNK cell populationK562 target cellsNK cellsRenal cell carcinomaAdvanced ccRCCNK cell clustersLocalized ccRCCAnti-tumor activityNormal kidneyNatural killerCell carcinomaMarkers of tissue residencyAdvanced renal cell carcinomaProportion of NK cellsFunction of NK cellsExpression of cytotoxic genesTarget cellsNK cell dysfunctionTotal immune cellsNK cell subsetsCell phenotypeCell populationsCell renal cell carcinomaDevelopment 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 carcinoma46 Radiological tumor burden is an independent risk factor for survival in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated with first line immunotherapy (IO)-based regimens
Nawfal R, Eid M, Semaan K, Paul M, Saliby R, Chehade R, Machaalani M, Phillips N, Canniff J, Saad E, Vasseur D, Zarif T, Yekeduz E, Sun M, Baca S, Braun D, Xie W, Krajewski K, Choueiri T. 46 Radiological tumor burden is an independent risk factor for survival in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated with first line immunotherapy (IO)-based regimens. The Oncologist 2024, 29: s25-s26. PMCID: PMC11301862, DOI: 10.1093/oncolo/oyae181.041.Peer-Reviewed Original ResearchIO-based regimensTumor burdenOverall survivalTreatment failureMultivariate analysisPrognostic factorsCT scanMetastatic clear cell renal cell carcinomaAssociated with treatment failureMultivariate Cox regression modelClear cell renal cell carcinomaHistory of nephrectomyIMDC risk groupsImmunotherapy-based regimensAssociated with OSMedian follow-upCell renal cell carcinomaDana-Farber Cancer InstituteLog-rank testIndependent risk factorRenal cell carcinomaKaplan-Meier curvesCT scan reportsManagement of patientsCox regression models24 Applying genomic analysis to refine unclassified renal cell carcinoma
Yekeduz E, Braun D, Chehade R, Eid M, Labaki C, Machaalani M, Nassar A, Nawfal R, Saad E, Saliby R, Semaan K, Sun M, Hirsch M, Ürün Y, Zarif T, Choueiri T. 24 Applying genomic analysis to refine unclassified renal cell carcinoma. The Oncologist 2024, 29: s20-s20. PMCID: PMC11301928, DOI: 10.1093/oncolo/oyae181.032.Peer-Reviewed Original ResearchRenal cell carcinomaClear cell RCCRenal cell carcinoma subtypesAmerican Association for Cancer ResearchPapillary RCCGenomic alterationsOverall survivalNF2 alterationsCell carcinomaGenomic profilingPapillary renal cell carcinomaSubtype of renal cell carcinomaChromophobe renal cell carcinomaProportion of female patientsClear cell renal cell carcinomaMedian overall survivalCell renal cell carcinomaFrequent genomic alterationsCo-mutated genesCompare categorical variablesBenjamini-Hochberg correctionOncogenic signaling pathwaysMetastatic sitesFrequent subtype of renal cell carcinomaPrimary tumor44 Liquid biopsy epigenomic profiling for the detection of sarcomatoid renal cell carcinoma
Semaan K, Zarif T, Eid M, Canniff J, Phillips N, Fortunato B, Savignano H, Davidson M, Chehade R, Garinet S, Saad E, Saliby R, Sun M, Seo J, Berchuck J, Braun D, Freedman M, Choueiri T, Baca S. 44 Liquid biopsy epigenomic profiling for the detection of sarcomatoid renal cell carcinoma. The Oncologist 2024, 29: s4-s5. PMCID: PMC11301903, DOI: 10.1093/oncolo/oyae181.006.Peer-Reviewed Original ResearchRenal cell carcinomaCell-free DNASarcomatoid differentiationRegulatory elementsArea under the receiver operating characteristicCell carcinomaChIP-seqResponse to immune checkpoint blockadeSarcomatoid renal cell carcinomaHistological subtypes of cancerAssociated with poor survivalImmune checkpoint blockadeDana-Farber Cancer InstituteChIP-seq signalsHistone modification signalsActive regulatory elementsArea under the receiver operating characteristic curveWilcoxon rank sum testTissue samplesCell-free chromatinRank sum testReceiver operating characteristicCheckpoint blockadeFrozen tissue samplesEpithelioid subtype45 INTerpath-004: A phase 2, randomized, double-blind study of pembrolizumab with V940 (mRNA-4157) or placebo in the adjuvant treatment of renal cell carcinoma
Choueiri T, Powles T, Braun D, Fong L, George D, Haas N, McDermott D, Shuch B, Gurney H, Meehan R, Posadas T, Wu S, Elfiky A, Motzer R. 45 INTerpath-004: A phase 2, randomized, double-blind study of pembrolizumab with V940 (mRNA-4157) or placebo in the adjuvant treatment of renal cell carcinoma. The Oncologist 2024, 29: s15-s15. PMCID: PMC11301864, DOI: 10.1093/oncolo/oyae181.022.Peer-Reviewed Original ResearchRenal cell carcinomaWeeks prior to randomizationAdverse eventsAdjuvant treatmentCell carcinomaResection of metastatic lesionsAdjuvant treatment of patientsPD-1 inhibitor pembrolizumabIncreased risk of recurrenceAdjuvant treatment of renal cell carcinomaTreatment of renal cell carcinomaActivity of pembrolizumabStage III/IV melanomaStudy of pembrolizumabDisease-free survivalMetastasis-free survivalPhase 2 trialRisk of recurrenceDouble-blind studyTreatment of patientsNovel combination strategiesDose of treatmentAdjuvant pembrolizumabAdjuvant settingInhibitor pembrolizumabEpigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma
El Zarif T, Semaan K, Eid M, Seo J, Garinet S, Davidsohn M, Sahgal P, Fortunato B, Canniff J, Nassar A, Abou Alaiwi S, Bakouny Z, Lakshminarayanan G, Savignano H, Lyons K, Matar S, Ali A, Saad E, Saliby R, Cordeiro P, Zhang Z, El Ahmar N, Laimon Y, Labaki C, Shah V, Freeman D, O'Toole J, Lee G, Hwang J, Pomerantz M, Signoretti S, Van Allen E, Xie W, Berchuck J, Viswanathan S, Braun D, Choueiri T, Freedman M, Baca S. Epigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma. Cell Reports 2024, 43: 114350. PMID: 38870013, DOI: 10.1016/j.celrep.2024.114350.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsRenal cell carcinomaSarcomatoid differentiationCell carcinomaResponse to immune checkpoint inhibitorsGene regulatory programsAssociated with poor survivalTreatment of renal cell carcinomaLow diagnostic yieldRandomized clinical trialsCheckpoint inhibitorsTumor histologyEpigenomic signaturesTranscription factor FOSL1Healthy volunteersPatient plasmaPoor survivalLiquid biopsyFOSL1 expressionClinical trialsProfiling histone modificationsDiagnostic approachImprove outcomesRegulatory programsPlasma samplesEmerging Novel Functional Imaging and Immunotherapy in Renal Cell Carcinoma and Current Treatment Sequencing Strategies After Immunotherapy.
Ali M, Eid M, Saliby R, Choi S, McKay R, Siva S, Braun D, Chen Y. Emerging Novel Functional Imaging and Immunotherapy in Renal Cell Carcinoma and Current Treatment Sequencing Strategies After Immunotherapy. American Society Of Clinical Oncology Educational Book 2024, 44: e438658. PMID: 38875505, DOI: 10.1200/edbk_438658.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaTreatment sequencing strategiesCell carcinomaImmune checkpoint inhibitors targeting PD-1Chimeric antigen receptor T-cell therapyCheckpoint inhibitors targeting PD-1Management of renal cell carcinomaAdvanced renal cell carcinomaProstate-specific membrane antigenLandscape of renal cell carcinomaRCC-associated antigensImmune checkpoint inhibitionT-cell therapyPrimary kidney tumorsAssess treatment responseChanging treatment landscapeCarbonic anhydrase IXFunctional imagingFunctional imaging modalitiesCheckpoint inhibitionPD-1Immunotherapy strategiesLAG-3Membrane antigenT cellsInvestigation of T cell phenotypes associated with response or resistance to immune checkpoint inhibitors (ICI) through single-cell analysis of renal cell carcinoma (RCC).
Kashima S, Ye Z, Meliki A, Hugaboom M, Schindler N, Graham J, Moritz V, El Ahmar N, Nabil Laimon Y, Canniff J, Saliby R, Lee G, Machaalani M, Sun M, Xu W, Signoretti S, McGregor B, McKay R, CHOUEIRI T, Braun D. Investigation of T cell phenotypes associated with response or resistance to immune checkpoint inhibitors (ICI) through single-cell analysis of renal cell carcinoma (RCC). Journal Of Clinical Oncology 2024, 42: 4515-4515. DOI: 10.1200/jco.2024.42.16_suppl.4515.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsRenal cell carcinomaCD8+ T cell infiltrationT cell infiltrationNon-respondersTumor microenvironmentT cellsRCC tumor microenvironmentResistance to immune checkpoint inhibitorsICI responseImmune checkpoint inhibitor treatmentImmune checkpoint inhibitor efficacyCD8+ T cellsExpressed PD-1ICI-treated patientsGene programGene signature scoresTumor mutation loadCellular compositionGene expression signaturesSingle-cell transcriptome analysisCheckpoint inhibitorsPD-1Partial responseSystemic therapyApplying genomic analysis to refine unclassified renal cell carcinoma.
Yekeduz E, Braun D, El Hajj Chehade R, Eid M, Labaki C, Machaalani M, Nassar A, Nawfal R, Saad E, Saliby R, Semaan K, Sun M, Hirsch M, Ürün Y, El Zarif T, CHOUEIRI T. Applying genomic analysis to refine unclassified renal cell carcinoma. Journal Of Clinical Oncology 2024, 42: 4551-4551. DOI: 10.1200/jco.2024.42.16_suppl.4551.Peer-Reviewed Original ResearchRenal cell carcinomaClear cell RCCRenal cell carcinoma subtypesAmerican Association for Cancer ResearchPapillary RCCGenomic alterationsOverall survivalCell carcinomaGenomic profilingPapillary renal cell carcinomaSubtype of renal cell carcinomaChromophobe renal cell carcinomaProportion of female patientsClear cell renal cell carcinomaMedian overall survivalCell renal cell carcinomaCo-mutated genesCompare categorical variablesBenjamini-Hochberg correctionOncogenic signaling pathwaysMetastatic sitesFrequent subtype of renal cell carcinomaPrimary tumorChi-square testNF2 alterationsMolecular analysis of the HCRN GU16-260-Cohort A phase II study of first-line (1L) nivolumab (nivo) and salvage nivo + ipilimumab (ipi) in patients (pts) with advanced clear cell renal cell carcinoma (accRCC).
Zaemes J, Hugaboom M, Shah V, Haas N, McDermott D, Jegede O, Bilen M, Stein M, Sosman J, Alter R, Plimack E, Hurwitz M, Wu C, Einstein D, Hammers H, Signoretti S, West D, Denize T, Atkins M, Braun D. Molecular analysis of the HCRN GU16-260-Cohort A phase II study of first-line (1L) nivolumab (nivo) and salvage nivo + ipilimumab (ipi) in patients (pts) with advanced clear cell renal cell carcinoma (accRCC). Journal Of Clinical Oncology 2024, 42: 4546-4546. DOI: 10.1200/jco.2024.42.16_suppl.4546.Peer-Reviewed Original ResearchObjective response rateImmune checkpoint blockadeProgression-free survivalProgressive diseaseAnti-VEGFOverall survivalAssociated with higher progression-free survivalTumor samplesAdvanced clear cell renal cell carcinomaCombined immune checkpoint blockadeHigher progression-free survivalIncreased PFSImmune checkpoint blockade therapyShorter progression-free survivalClear cell renal cell carcinomaAnti-VEGF therapyCell renal cell carcinomaWeeks of therapyRenal cell carcinomaBiomarkers of efficacyFFPE tumor samplesNIVO monotherapyCheckpoint blockadeDecreased OSProspective trialsExpression 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 stainingAdvanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587).
Serzan M, Jegede O, Alter R, Bilen M, Braun D, Einstein D, Haas N, Herchenhorn D, King J, Runcie K, Sosman J, Sternberg C, Yang Y, Signoretti S, CHOUEIRI T, Atkins M. Advanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587). Journal Of Clinical Oncology 2024, 42: tps4614-tps4614. DOI: 10.1200/jco.2024.42.16_suppl.tps4614.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsArm BArm APrimary endpointRate of immune-related adverse eventsMetastatic clear cell renal cell carcinomaImmune-related adverse eventsMolecular predictors of responseVEGF receptor tyrosine kinase inhibitorReceptor tyrosine kinase inhibitorsEnhance T cell primingOne-sided significance levelClear cell renal cell carcinomaAnti-PD1 inhibitorsIMDC risk groupsTreatment free intervalProgression-free survivalT cell primingTreatment-free survivalCell renal cell carcinomaSubpopulations of TregsFirst-line treatmentRenal cell carcinomaPredictors of responseAssociated with increased presenceIntratumoral T-cell infiltration and response to nivolumab plus ipilimumab in patients with metastatic clear cell renal cell carcinoma from the CheckMate-214 trial.
Matar S, Jegede O, Denize T, Ghandour F, Nabil Laimon Y, El Ahmar N, Bagheri Sheshdeh A, Savla V, Mohanna R, Catalano P, Braun D, Sun M, Gupta S, Vemula S, Freeman G, Motzer R, Atkins M, McDermott D, CHOUEIRI T, Signoretti S. Intratumoral T-cell infiltration and response to nivolumab plus ipilimumab in patients with metastatic clear cell renal cell carcinoma from the CheckMate-214 trial. Journal Of Clinical Oncology 2024, 42: 4536-4536. DOI: 10.1200/jco.2024.42.16_suppl.4536.Peer-Reviewed Original ResearchProgression-free survivalAssociated with progression-free survivalMultiplex immunofluorescenceClinical trialsClinical outcomesMetastatic clear cell renal cell carcinomaIntratumoral T cell infiltrationTreated with nivolumab monotherapyMetastatic clear cell RCCClear cell renal cell carcinomaResponse to nivolumabT cell infiltrationCell renal cell carcinomaPoor-risk patientsRenal cell carcinomaClear cell RCCFormalin fixed paraffinContinuous variablesNivolumab monotherapyCox proportional hazardsAntigen-experiencedCell RCCCell carcinomaLogistic regression modelsPositive association