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 microarrayUpdate 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
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 ResearchMeSH KeywordsBrain NeoplasmsCarcinoma, Renal CellHepatitis A Virus Cellular Receptor 2HumansImmune System DiseasesKidney NeoplasmsMedical OncologyTumor MicroenvironmentConceptsRenal 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 samplesOutcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma
Dizman N, Austin M, Considine B, Jessel S, Schoenfeld D, Merl M, Hurwitz M, Sznol M, Kluger H. Outcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma. Clinical Genitourinary Cancer 2023, 21: 221-229. PMID: 36681606, DOI: 10.1016/j.clgc.2023.01.002.Peer-Reviewed Original ResearchMeSH KeywordsAxitinibCarcinoma, Renal CellHumansKidney NeoplasmsProspective StudiesRetrospective StudiesVascular Endothelial Growth Factor AConceptsMetastatic renal cell carcinomaPembrolizumab/axitinibObjective response rateProgression-free survivalImmune checkpoint inhibitorsMedian progression-free survivalAdverse eventsRenal cell carcinomaCell carcinomaClear cell metastatic renal cell carcinomaVascular endothelial growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsCombination immune checkpoint inhibitorsGrade 5 adverse eventsPrior immune checkpoint inhibitorsSuperior progression-free survivalReceptor tyrosine kinase inhibitorsYale-New Haven HospitalFurther-line treatmentNivolumab/ipilimumabRECIST 1.1 criteriaResponse-evaluable patientsDisease control rateSecond-line therapyFirst-line treatment
2022
Loss of PBRM1 alters promoter histone modifications and activates ALDH1A1 to drive renal cell carcinomaPBRM1 loss increases H3K4me3 marks and expression of ALDH1A1
Schoenfeld D, Zhou R, Zairis S, Su W, Steinbach N, Mathur D, Bansal A, Zachem A, Tavarez B, Hasson D, Bernstein E, Rabadan R, Parsons R. Loss of PBRM1 alters promoter histone modifications and activates ALDH1A1 to drive renal cell carcinomaPBRM1 loss increases H3K4me3 marks and expression of ALDH1A1. Molecular Cancer Research 2022, 20: 1193-1207. PMID: 35412614, PMCID: PMC9357026, DOI: 10.1158/1541-7786.mcr-21-1039.Peer-Reviewed Original ResearchConceptsRetinoic acid biosynthesisSuch target genesPromoter histone modificationsAcid biosynthesisHistone modificationsClear cell renal cell carcinomaTarget genesLoss of PBRM1SWI/SNF complexSWI/SNF chromatinSWI/SNF subunitsHistone modification ChIP-seqSWI/SNF componentsATAC-seq dataCcRCC cell linesDe novo gainPBAF subunitsH3K4me3 peaksH3K4me3 marksPBAF complexSNF complexEpigenomic approachesChIP-seqRNA-seqHigh mutation frequency