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 microarrayDevelopment 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 carcinomaPathological concordance rate and outcomes by subtype in advanced papillary renal cell carcinoma
Tripathi A, Tangen C, Plets M, Li X, Tretiakova M, Humphrey P, Adeniran A, Barata P, Gulati S, Bergerot C, Pruthi D, Thompson I, Lara P, Lerner S, Pal S, Shuch B. Pathological concordance rate and outcomes by subtype in advanced papillary renal cell carcinoma. BJU International 2024 PMID: 39014969, DOI: 10.1111/bju.16403.Peer-Reviewed Original ResearchPapillary renal cell carcinomaPositive predictive valueRenal cell carcinomaLocal pathology reviewCentral reviewPathology reviewCell carcinomaAdvanced papillary renal cell carcinomaMetastatic papillary renal cell carcinomaPapillary renal cell carcinoma subtypesPatients treated with targeted therapyExpert genitourinary pathologistsPathological concordance rateLocal reviewGenitourinary pathologistsClinical benefitCabozantinibClinical significanceClinical valueSubtype assignmentConcordance rateType 1CarcinomaPatientsPredictive valueSarcomatoid and Rhabdoid Renal Cell Carcinoma
Adeniran A, Shuch B, Humphrey P. Sarcomatoid and Rhabdoid Renal Cell Carcinoma. The American Journal Of Surgical Pathology 2024, 48: e65-e88. PMID: 38736105, DOI: 10.1097/pas.0000000000002233.Peer-Reviewed Original ResearchRenal cell carcinomaSarcomatoid renal cell carcinomaGenomic alterationsRhabdoid differentiationRhabdoid cellsCell carcinomaWHO classification of renal tumorsClassification of renal tumorsInternational Collaboration on Cancer ReportingHistologic types of renal cell carcinomaPleomorphic undifferentiated sarcomaMalignant spindle cellsAggressive biological behaviorMolecular featuresMolecular mechanisms of tumorigenesisMechanisms of tumorigenesisSarcomatoid growthRhabdoid componentSarcomatoid componentRhabdoid featuresRenal tumorsClinical responseCollege of American PathologistsRhabdoid morphologySarcomatoid elements
2023
Immune 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 samplesPathologic concordance rate and outcomes by histologic subtype in advanced papillary renal cell (pRCC) carcinoma: An analysis from the SWOG S1500 (PAPMET) trial.
Tripathi A, Tangen C, Li X, Tretiakova M, Humphrey P, Adeniran A, Barata P, Gulati S, Bergerot C, Pruthi D, Thompson I, Lara P, Pal S, Shuch B. Pathologic concordance rate and outcomes by histologic subtype in advanced papillary renal cell (pRCC) carcinoma: An analysis from the SWOG S1500 (PAPMET) trial. Journal Of Clinical Oncology 2023, 41: 4562-4562. DOI: 10.1200/jco.2023.41.16_suppl.4562.Peer-Reviewed Original ResearchProgression-free survivalPositive predictive valueCentral pathology reviewCentral reviewPathology reviewHistologic subtypeType 1PRCC subtypesAdvanced papillary renal cell carcinomaPathologic concordance rateLines of therapyPapillary renal cell carcinomaSubset of patientsType 2 tumorGreater clinical benefitRenal cell carcinomaLimited clinical valueType 2 diseaseExpert genitourinary pathologistsLocal reviewClassification of subtypesSunitinib armMET alterationsClinical outcomesClinical benefit
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 therapy
2021
Sunitinib versus cabozantinib, crizotinib or savolitinib in metastatic papillary renal cell carcinoma (pRCC): Results from the randomized phase II SWOG 1500 study.
Pal S, Tangen C, Thompson I, Haas N, George D, Heng D, Shuch B, Stein M, Tretiakova M, Humphrey P, Adeniran A, Narayan V, Bjarnason G, Vaishampayan U, Alva A, Zhang T, Cole S, Plets M, Wright J, Lara P. Sunitinib versus cabozantinib, crizotinib or savolitinib in metastatic papillary renal cell carcinoma (pRCC): Results from the randomized phase II SWOG 1500 study. Journal Of Clinical Oncology 2021, 39: 270-270. DOI: 10.1200/jco.2021.39.6_suppl.270.Peer-Reviewed Original ResearchMetastatic papillary renal cell carcinomaPapillary renal cell carcinomaProgression-free survivalMedian progression-free survivalEligible patientsPO QDPrior therapyOverall survivalAdverse eventsGrade 5 adverse eventsZubrod performance status 0Measurable metastatic diseasePerformance status 0Randomized phase IIRenal cell carcinomaMET kinase inhibitorType IMeaningful prolongationPo bidStatus 0Secondary endpointsMetastatic diseasePathologic reviewPFS eventsSystemic therapy
2016
Racial disparities in renal cell carcinoma: a single‐payer healthcare experience
Mafolasire A, Yao X, Nawaf C, Suarez‐Sarmiento A, Chow W, Zhao W, Corley D, Hofmann JN, Purdue M, Adeniran AJ, Shuch B. Racial disparities in renal cell carcinoma: a single‐payer healthcare experience. Cancer Medicine 2016, 5: 2101-2108. PMID: 27228559, PMCID: PMC4884637, DOI: 10.1002/cam4.755.Peer-Reviewed Original ResearchConceptsDisease-specific survivalRenal cell carcinomaBlack patientsIndependent predictorsSurgical treatmentWhite patientsCell carcinomaRacial disparitiesKaiser Permanente Northern California systemWorse disease-specific survivalCox proportion hazard modelAdvanced American Joint CommitteePapillary renal cell carcinomaKaplan-Meier methodProportion hazard modelAmerican Joint CommitteeLarger tumor sizeCase-control studyHealthcare systemSingle-payer healthcare systemSingle healthcare systemSignificant racial disparitiesOverall survivalPatient demographicsDifferent comorbiditiesGenomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma
Bi M, Zhao S, Said JW, Merino MJ, Adeniran AJ, Xie Z, Nawaf CB, Choi J, Belldegrun AS, Pantuck AJ, Kluger HM, Bilgüvar K, Lifton RP, Shuch B. Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 2170-2175. PMID: 26864202, PMCID: PMC4776463, DOI: 10.1073/pnas.1525735113.Peer-Reviewed Original ResearchMeSH KeywordsAgedCarcinoma, Renal CellCell DedifferentiationDNA Mismatch RepairDNA-Binding ProteinsExomeFemaleGenes, p53HumansKidney NeoplasmsLoss of HeterozygosityMaleMiddle AgedMutationNuclear ProteinsOncogenesPolymorphism, Single NucleotidePrognosisTranscription FactorsTumor Suppressor ProteinsUbiquitin ThiolesteraseConceptsClear cell renal cell carcinomaCell renal cell carcinomaRenal cell carcinomaSarcomatoid elementsCarcinomatous elementsCell carcinomaSomatic single nucleotide variantsVon Hippel-Lindau tumor suppressorPoor-prognosis cancerTreatment of patientsTumor protein p53 (TP53) mutationsMismatch repair deficiencyRich interaction domain 1ASarcomatoid featuresPoor prognosisUnknown pathogenesisPolybromo-1TP53 mutationsP53 mutationsSarcomatoid transformationPan-cancer genesExome sequencingTumorsRepair deficiencyProtein 1The incidence of adverse pathologic characteristics in small renal masses as size increases.
Nawaf C, Rosoff J, Adeniran A, Humphrey P, Shuch B. The incidence of adverse pathologic characteristics in small renal masses as size increases. Journal Of Clinical Oncology 2016, 34: 596-596. DOI: 10.1200/jco.2016.34.2_suppl.596.Peer-Reviewed Original ResearchAdverse pathologic featuresRenal cell carcinomaActive surveillanceLymphovascular invasionPathologic featuresRenal massesAdverse pathologic characteristicsCT1a renal massesHistologic tumor necrosisRenal tumor biopsySelection of patientsSingle-institution databaseType II histologyHigh nuclear gradeTumor size categoriesSmall renal massesSignificant increaseSarcomatoid featuresPathologic characteristicsTumor sizeCell carcinomaPrimary tumorAUA guidelinesHistologic characteristicsLarge tumorsGenomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma.
Bi X, Zhao S, Adeniran A, Kluger H, Xie Z, Nawaf C, Merino M, Valera V, Pantuck A, Said J, Belldegrun A, Lifton R, Shuch B. Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma. Journal Of Clinical Oncology 2016, 34: 509-509. DOI: 10.1200/jco.2016.34.2_suppl.509.Peer-Reviewed Original ResearchDriver genesCancer driver genesSomatic mutationsProtein traffickingIllumina sequencingSomatic cellsGenomic characterizationCell differentiationCell adhesionLoss of heterozygosityClear cell renal cell carcinomaGenesMutational signaturesCell renal cell carcinomaClonal divergenceGenetic alterationsMutationsTP53 mutationsRepair deficiencySarcomatoid transformationSubset of tumorsCcRCCHypermutationRenal cell carcinomaBAP1