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 model582 Spatial profiling reveals architecture difference between primary and lung metastatic ccRCC
Wang Y, Cho J, Laimon Y, Sheshdeh A, Murugan N, Yuan H, Wee J, Xu W, Braun D, Choueiri T, Wu C, Signoretti S, Freeman G, Hemberg M, Marasco W. 582 Spatial profiling reveals architecture difference between primary and lung metastatic ccRCC. 2024, a662-a662. DOI: 10.1136/jitc-2024-sitc2024.0582.Peer-Reviewed Original ResearchRechallenging with anti-PD-1 therapy in advanced renal cell carcinoma
Yochum Z, Braun D. Rechallenging with anti-PD-1 therapy in advanced renal cell carcinoma. The Lancet 2024, 404: 1280-1282. PMID: 39284326, DOI: 10.1016/s0140-6736(24)01866-x.Peer-Reviewed Original ResearchClinical Implications of Basic Research: Exploring the Transformative Potential of Spatial 'Omics in Uro-oncology
Figiel S, Bates A, Braun D, Eapen R, Eckstein M, Manley B, Milowsky M, Mitchell T, Bryant R, Sfakianos J, Lamb A. Clinical Implications of Basic Research: Exploring the Transformative Potential of Spatial 'Omics in Uro-oncology. European Urology 2024 PMID: 39227262, DOI: 10.1016/j.eururo.2024.08.025.Peer-Reviewed Original ResearchComputational analysis workflowMolecular dataTreatment of urological cancersGenetic changesHarmonisation of protocolsMolecular technologiesPersonalised cancer therapyCellular variationDisease developmentSpatial omicsTumor microenvironmentRisk stratificationUrological cancersCancer developmentAnalysis workflowPrecision medicineIndividual malignanciesReagent costsCancer therapyUro-oncologyCancer tissuesTumorTissue architectureClinical implicationsCancer1705P 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 Research176P ERBB2 amplifications across sex, race, and cancer types
Machaalani M, Chehade R, Nassar A, Zarif T, Saad E, Yekeduz E, Saliby R, Steiner C, Nawfal R, Semaan K, Eid M, Lee G, Pomerantz M, McKay R, Tarantino P, Braun D, Sun M, Tolaney S, Choueiri T. 176P ERBB2 amplifications across sex, race, and cancer types. Annals Of Oncology 2024, 35: s285-s286. DOI: 10.1016/j.annonc.2024.08.2181.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 Research1694MO Novel serum glycoproteomic biomarkers predict response to nivolumab plus cabozantinib (NIVO+CABO) versus sunitinib (SUN) in advanced RCC (aRCC): Analysis from CheckMate 9ER
Braun D, Wang Y, Yu A, Pickering C, Serie D, Choueiri T, Xu W, Sun M, Vemula S, Gupta S. 1694MO Novel serum glycoproteomic biomarkers predict response to nivolumab plus cabozantinib (NIVO+CABO) versus sunitinib (SUN) in advanced RCC (aRCC): Analysis from CheckMate 9ER. Annals Of Oncology 2024, 35: s1012-s1013. DOI: 10.1016/j.annonc.2024.08.1787.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 ResearchSystematic identification of minor histocompatibility antigens predicts outcomes of allogeneic hematopoietic cell transplantation
Cieri N, Hookeri N, Stromhaug K, Li L, Keating J, Díaz-Fernández P, Gómez-García de Soria V, Stevens J, Kfuri-Rubens R, Shao Y, Kooshesh K, Powell K, Ji H, Hernandez G, Abelin J, Klaeger S, Forman C, Clauser K, Sarkizova S, Braun D, Penter L, Kim H, Lane W, Oliveira G, Kean L, Li S, Livak K, Carr S, Keskin D, Muñoz-Calleja C, Ho V, Ritz J, Soiffer R, Neuberg D, Stewart C, Getz G, Wu C. Systematic identification of minor histocompatibility antigens predicts outcomes of allogeneic hematopoietic cell transplantation. Nature Biotechnology 2024, 1-12. PMID: 39169264, DOI: 10.1038/s41587-024-02348-3.Peer-Reviewed Original ResearchAllogeneic hematopoietic cell transplantationHematopoietic cell transplantationCell transplantationEffect of allogeneic hematopoietic cell transplantationIdentification of minor histocompatibility antigensOutcomes of allogeneic hematopoietic cell transplantationOccurrence of acute GVHDPost-transplant disease recurrenceGraft-versus-host diseaseWhole-exome sequencing of germline DNASequencing of germline DNAGraft-versus-leukemiaT-cell alloreactivityGraft-versus-hostMinor histocompatibility antigensWhole-exome sequencingAcute GVHDPulmonary GVHDAllo-HCTDisease recurrenceHistocompatibility antigensClinical outcomesValidation cohortGermline DNAGVHDFirst-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 carcinoma20 Evaluating intermediate endpoints for overall survival in metastatic renal cell carcinoma treated with immune checkpoint inhibitors: an IMDC study
Saliby R, Xie W, Wells C, Saad E, Eid M, Semaan K, Labaki C, Ferrier E, Zarba M, Ebrahimi H, Ravi P, Suarez C, Morales J, McKay R, Powles T, Wood L, Lalani A, Pal S, de Velasco G, Takemura K, Agarwal N, Braun D, Heng D, Choueiri T. 20 Evaluating intermediate endpoints for overall survival in metastatic renal cell carcinoma treated with immune checkpoint inhibitors: an IMDC study. The Oncologist 2024, 29: s8-s9. PMCID: PMC11301915, DOI: 10.1093/oncolo/oyae181.013.Peer-Reviewed Original ResearchTime to next therapyInternational mRCC Database ConsortiumTime to treatment failureInternational mRCC Database Consortium risk groupOverall survivalObjective responseFollow-upIndividual patient dataLandmark analysisTreatment failureInternational Metastatic Renal-Cell Carcinoma Database ConsortiumMetastatic renal cell carcinoma treated with immune checkpoint inhibitorsRisk groupsEndpoint of overall survivalMonths of follow-upIntermediate endpointsICI-based regimensImmune checkpoint inhibitorsImmune-checkpoint inhibitorsMedian follow-upAnalysis of OSAssociated with OSAssociation of OSPost-therapy initiationFollow-up time46 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 models22 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 inhibitors24 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 pembrolizumab