2024
TIGIT 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 microarrayEmerging 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 cellsImpact of renal cell carcinoma molecular subtypes on immunotherapy and targeted therapy outcomes
Saliby R, Labaki C, Jammihal T, Xie W, Sun M, Shah V, Saad E, Kane M, Kashima S, Sadak K, El Zarif T, Poduval D, Motzer R, Powles T, Rini B, Albiges L, Pal S, McGregor B, McKay R, Signoretti S, Van Allen E, Shukla S, Choueiri T, Braun D. Impact of renal cell carcinoma molecular subtypes on immunotherapy and targeted therapy outcomes. Cancer Cell 2024, 42: 732-735. PMID: 38579722, PMCID: PMC11130783, DOI: 10.1016/j.ccell.2024.03.002.Peer-Reviewed Original ResearchUpdate 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 StatementsMeSH KeywordsBiomarkersBiomedical ResearchCarcinoma, Renal CellGene Expression ProfilingHumansKidney NeoplasmsConceptsRenal 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
Spatially aware deep learning reveals tumor heterogeneity patterns that encode distinct kidney cancer states
Nyman J, Denize T, Bakouny Z, Labaki C, Titchen B, Bi K, Hari S, Rosenthal J, Mehta N, Jiang B, Sharma B, Felt K, Umeton R, Braun D, Rodig S, Choueiri T, Signoretti S, Van Allen E. Spatially aware deep learning reveals tumor heterogeneity patterns that encode distinct kidney cancer states. Cell Reports Medicine 2023, 4: 101189. PMID: 37729872, PMCID: PMC10518628, DOI: 10.1016/j.xcrm.2023.101189.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionClear cell renal cell carcinomaCell renal cell carcinomaRenal cell carcinomaTumor immune stateCcRCC biologyICI responseTumor-immune interactionsCheckpoint inhibitionCell carcinomaImmune infiltrationPatient outcomesPathologist's analysisImmune featuresCcRCC tumorsTumor phenotypeTumorsModels of tumorWhole slide imagesImmune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases
Schoenfeld D, Moutafi M, Martinez S, Djureinovic D, Merkin R, Adeniran A, Braun D, Signoretti S, Choueiri T, Parisi F, Hurwitz M, Rimm D, Wei W, Jilaveanu L, Kluger H. Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases. Journal For ImmunoTherapy Of Cancer 2023, 11: e007240. PMID: 37586773, PMCID: PMC10432651, DOI: 10.1136/jitc-2023-007240.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaBrain metastasesPrimary tumorTumor microenvironmentDigital spatial profilingCell carcinomaActivation protein expressionInflammatory macrophage markersRCC brain metastasesInnate immune activatorsNormal kidney samplesProgressive stagesExtracranial metastasesTim-3Immune checkpointsImmune dysfunctionImmune activationRCC metastasisLonger survivalImmune activatorsMacrophage markersTreatment responseSeparate cohortTissue microarrayMetastatic samplesChromophobe renal cell carcinoma
Henske E, Cheng L, Hakimi A, Choueiri T, Braun D. Chromophobe renal cell carcinoma. Cancer Cell 2023, 41: 1383-1388. PMID: 37541245, DOI: 10.1016/j.ccell.2023.07.006.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsBiomarkers, TumorCarcinoma, Renal CellHumansImmunity, InnateKidney NeoplasmsLymphocytesOxidative StressConceptsChromophobe renal cell carcinomaClear cell RCCRenal cell carcinomaCell carcinomaCell/ILTerms of geneticsCell of originImmune therapyCell RCCTargetable pathwaysMTOR inhibitorsMitochondrial dysfunctionPathway mutationsOxidative stressPotential mechanismsChRCCCarcinomaCurrent dataRCCGenomicsKinaseImmunotherapyResponseDysfunctionGeneticsEmerging Biomarkers of Response to Systemic Therapies in Metastatic Clear Cell Renal Cell Carcinoma
Labaki C, Saliby R, Bakouny Z, Saad E, Semaan K, Eid M, Lalani A, Choueiri T, Braun D. Emerging Biomarkers of Response to Systemic Therapies in Metastatic Clear Cell Renal Cell Carcinoma. Hematology/Oncology Clinics Of North America 2023, 37: 937-942. PMID: 37407357, DOI: 10.1016/j.hoc.2023.05.021.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMetastatic clear cell renal cell carcinomaClear cell renal cell carcinomaCell renal cell carcinomaRenal cell carcinomaSystemic therapyCell carcinomaImmunotherapy-based regimensBiomarkers of responseSystemic regimensClinical responseValid biomarkersPromising biomarkerHeterogeneous outcomesTherapyBiomarkersRegimensPatientsCarcinomaMccRCCResponseNovel Targeted Therapies for Renal Cell Carcinoma Building on the Successes of Vascular Endothelial Growth Factor and mTOR Inhibition
Saliby R, Saad E, Labaki C, Xu W, Braun D, Viswanathan S, Bakouny Z. Novel Targeted Therapies for Renal Cell Carcinoma Building on the Successes of Vascular Endothelial Growth Factor and mTOR Inhibition. Hematology/Oncology Clinics Of North America 2023, 37: 1015-1026. PMID: 37385938, DOI: 10.1016/j.hoc.2023.05.022.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsCarcinoma, Renal CellHumansKidney NeoplasmsTOR Serine-Threonine KinasesVascular Endothelial Growth Factor AConceptsRenal cell carcinomaTreatment of RCCTargeted therapyNovel Targeted TherapiesVHL/HIF pathwayVascular endothelial growth factorEndothelial growth factorCell carcinomaMetabolic targetingMTOR inhibitionMTOR pathwayGrowth factorTherapyPromising novelHIF pathwayTreatmentOxygen homeostasisEpigenomic reprogrammingRemarkable advancesPathwayCarcinomaNovel 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 1ImmunotherapyPatientsCarcinomaImmunosuppressionTherapyCirculating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma
Saliby R, Zarif T, Bakouny Z, Shah V, Xie W, Flippot R, Denize T, Kane M, Madsen K, Ficial M, Hirsch L, Wei X, Steinharter J, Harshman L, Vaishampayan U, Severgnini M, McDermott D, Lee G, Xu W, Van Allen E, McGregor B, Signoretti S, Choueiri T, McKay R, Braun D. Circulating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma. Cancer Immunology Research 2023, 11: 1114-1124. PMID: 37279009, PMCID: PMC10526700, DOI: 10.1158/2326-6066.cir-22-0996.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenBevacizumabCarcinoma, Renal CellHumansKidney NeoplasmsVascular Endothelial Growth Factor AConceptsRenal cell carcinomaT cellsWorse PFSImmunotherapy responseCell carcinomaPeripheral immune cell populationsWorse progression-free survivalSarcomatoid renal cell carcinomaPhase II clinical trialImmunotherapy-based combinationsValue of tumourPoor-risk patientsProgression-free survivalImmune cell populationsVascular endothelial growth factorKidney cancer diagnosisEndothelial growth factorFuture biomarker studiesLack of responseInflammatory modulesExhausted CD8Variant histologyOverall survivalPD-L1Sarcomatoid differentiationImmunobiology and Metabolic Pathways of Renal Cell Carcinoma
Braun D, Chakraborty A. Immunobiology and Metabolic Pathways of Renal Cell Carcinoma. Hematology/Oncology Clinics Of North America 2023, 37: 827-840. PMID: 37246090, DOI: 10.1016/j.hoc.2023.04.012.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsCarcinoma, Renal CellHumansImmune Checkpoint InhibitorsKidney NeoplasmsMetabolic Networks and PathwaysConceptsRenal cell carcinomaCell carcinomaAdvanced renal cell carcinomaClear cell renal cell carcinomaImmune checkpoint inhibitorsCell renal cell carcinomaNew treatment targetsFuture clinical developmentCheckpoint inhibitorsNovel therapeutic developmentDurable responsesMost patientsMetabolic dysregulationDistinct tumorsClinical developmentImmune pathwaysTreatment targetsTherapeutic developmentCarcinomaCurrent understandingMetabolic pathwaysPatientsImmunobiologyTumorsPathwayThe Changing Landscape of Immunotherapy for Advanced Renal Cancer
Kashima S, Braun D. The Changing Landscape of Immunotherapy for Advanced Renal Cancer. Urologic Clinics Of North America 2023, 50: 335-349. PMID: 36948676, DOI: 10.1016/j.ucl.2023.01.012.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRenal cell carcinomaAdvanced renal cell carcinomaCell carcinomaCentral therapeutic strategyAdvanced renal cancerDurable clinical benefitImmune checkpoint inhibitorsImmunecheckpoint inhibitorsCheckpoint inhibitorsCytokine therapyImmunogenic tumorsMost patientsSystemic therapyClinical benefitCombination therapyCurrent therapiesInterleukin-2Renal cancerTherapeutic strategiesTherapyCarcinomaInhibitorsImmunotherapyPatientsInterferonEpigenomic charting and functional annotation of risk loci in renal cell carcinoma
Nassar A, Abou Alaiwi S, Baca S, Adib E, Corona R, Seo J, Fonseca M, Spisak S, El Zarif T, Tisza V, Braun D, Du H, He M, Flaifel A, Alchoueiry M, Denize T, Matar S, Acosta A, Shukla S, Hou Y, Steinharter J, Bouchard G, Berchuck J, O’Connor E, Bell C, Nuzzo P, Mary Lee G, Signoretti S, Hirsch M, Pomerantz M, Henske E, Gusev A, Lawrenson K, Choueiri T, Kwiatkowski D, Freedman M. Epigenomic charting and functional annotation of risk loci in renal cell carcinoma. Nature Communications 2023, 14: 346. PMID: 36681680, PMCID: PMC9867739, DOI: 10.1038/s41467-023-35833-5.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Renal CellEpigenomicsForkhead Transcription FactorsHumansKidney NeoplasmsOncogenesTranscription FactorsConceptsMaster transcription factorChIP-seqATAC-seq dataH3K27ac ChIP-seqCcRCC cell linesEpigenomic atlasATAC-seqFunctional annotationTranscriptional landscapePrimary human samplesTranscription factorsRNA-seqRisk lociTranscriptional upregulationSNP arrayRisk SNPsETS-1EpigenomeCell linesFOXI1Renal cell carcinomaEPAS1RCC histologic subtypesHuman samplesBHLHE41
2022
Transcriptomic Correlates of Tumor Cell PD-L1 Expression and Response to Nivolumab Monotherapy in Metastatic Clear Cell Renal Cell Carcinoma.
Denize T, Hou Y, Pignon J, Walton E, West D, Freeman G, Braun D, Wu C, Gupta S, Motzer R, Atkins M, McDermott D, Choueiri T, Shukla S, Signoretti S. Transcriptomic Correlates of Tumor Cell PD-L1 Expression and Response to Nivolumab Monotherapy in Metastatic Clear Cell Renal Cell Carcinoma. Clinical Cancer Research 2022, 28: 4045-4055. PMID: 35802667, PMCID: PMC9481706, DOI: 10.1158/1078-0432.ccr-22-0923.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, TumorCarcinoma, Renal CellHumansKidney NeoplasmsNivolumabTranscriptomeConceptsTC PD-L1 expressionClear cell renal cell carcinomaPD-L1 expressionMetastatic clear cell renal cell carcinomaCell renal cell carcinomaRenal cell carcinomaProliferation-related pathwaysCell proliferation-related pathwaysClinical outcomesTumor cellsCell carcinomaTumor cell PD-L1 expressionAnti-PD-1 monotherapyPD-L1 positive tumorsHigher objective response rateLonger progression-free survivalTumor-infiltrating immune cellsTC PD-L1Objective response ratePD-L1 statusProgression-free survivalT-cell activation signaturesCheckMate 025 trialNivolumab monotherapyPD-L1
2021
Progressive immune dysfunction with advancing disease stage in renal cell carcinoma
Braun DA, Street K, Burke KP, Cookmeyer DL, Denize T, Pedersen CB, Gohil SH, Schindler N, Pomerance L, Hirsch L, Bakouny Z, Hou Y, Forman J, Huang T, Li S, Cui A, Keskin DB, Steinharter J, Bouchard G, Sun M, Pimenta EM, Xu W, Mahoney KM, McGregor BA, Hirsch MS, Chang SL, Livak KJ, McDermott DF, Shukla SA, Olsen LR, Signoretti S, Sharpe AH, Irizarry RA, Choueiri TK, Wu CJ. Progressive immune dysfunction with advancing disease stage in renal cell carcinoma. Cancer Cell 2021, 39: 632-648.e8. PMID: 33711273, PMCID: PMC8138872, DOI: 10.1016/j.ccell.2021.02.013.Peer-Reviewed Original ResearchConceptsClear cell renal cell carcinomaM2-like macrophagesRenal cell carcinomaAdvanced diseaseExhausted CD8Cell carcinomaDisease stageAdvanced/metastaticImmune inhibitory pathwaysProgressive immune dysfunctionCell renal cell carcinomaAdjacent non-tumor tissuesTumor immune microenvironmentPro-inflammatory macrophagesM2-like polarizationNon-tumor tissuesMetastatic diseaseImmune dysfunctionWorse prognosisImmune microenvironmentImmune cellsCell dysfunctionExternal cohortInhibitory pathwaysMyeloid compartmentBeyond conventional immune-checkpoint inhibition — novel immunotherapies for renal cell carcinoma
Braun DA, Bakouny Z, Hirsch L, Flippot R, Van Allen EM, Wu CJ, Choueiri TK. Beyond conventional immune-checkpoint inhibition — novel immunotherapies for renal cell carcinoma. Nature Reviews Clinical Oncology 2021, 18: 199-214. PMID: 33437048, PMCID: PMC8317018, DOI: 10.1038/s41571-020-00455-z.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaImmune checkpoint inhibitorsCell carcinomaAdvanced stage renal cell carcinomaContext of RCCNovel immune-based therapiesAntigen-directed therapiesImmunotherapy-based combinationsSuccess of antibodiesAntitumour immune responseDurable clinical benefitImmune-based therapiesT cell infiltrationCancer-immunity cycleImmune-based treatmentsTreatment of patientsMost renal cell carcinomasTumor CD8Most patientsImmune checkpointsPD-1Innovative immunotherapiesTherapeutic vaccinesWorse prognosisClinical benefit
2020
Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma
Braun DA, Hou Y, Bakouny Z, Ficial M, Sant’ Angelo M, Forman J, Ross-Macdonald P, Berger AC, Jegede OA, Elagina L, Steinharter J, Sun M, Wind-Rotolo M, Pignon JC, Cherniack AD, Lichtenstein L, Neuberg D, Catalano P, Freeman GJ, Sharpe AH, McDermott DF, Van Allen EM, Signoretti S, Wu CJ, Shukla SA, Choueiri TK. Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma. Nature Medicine 2020, 26: 909-918. PMID: 32472114, PMCID: PMC7499153, DOI: 10.1038/s41591-020-0839-y.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntigen PresentationAntineoplastic Agents, ImmunologicalCarcinoma, Renal CellCD8-Positive T-LymphocytesChromosome DeletionChromosomes, Human, Pair 6Chromosomes, Human, Pair 9Class I Phosphatidylinositol 3-KinasesDNA-Binding ProteinsExome SequencingFemaleFluorescent Antibody TechniqueGene DeletionGenomicsHistocompatibility Antigens Class IIHistone DemethylasesHistone-Lysine N-MethyltransferaseHumansKidney NeoplasmsLymphocytes, Tumor-InfiltratingMaleMiddle AgedMutationNivolumabPrognosisProteasome Endopeptidase ComplexPTEN PhosphohydrolaseSequence Analysis, RNATOR Serine-Threonine KinasesTranscription FactorsTuberous Sclerosis Complex 1 ProteinTumor Suppressor ProteinsUbiquitin ThiolesteraseVon Hippel-Lindau Tumor Suppressor ProteinConceptsAdvanced clear cell renal cell carcinomaClear cell renal cell carcinomaPD-1 blockadeCell renal cell carcinomaRenal cell carcinomaCell carcinomaDegree of CD8Numerous chromosomal alterationsProspective clinical trialsSomatic alterationsInfiltrated tumorsClinical responseCell infiltrationTherapeutic responseClinical trialsTherapeutic efficacyBlockadeCcRCC tumorsTumorsPBRM1 mutationsModulates responseCD8Chromosomal alterationsImmunofluorescence analysisCarcinoma
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 ResearchMeSH KeywordsCarcinoma, Renal CellForecastingHumansImmunotherapyKidney NeoplasmsTranslational Research, BiomedicalConceptsRenal 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