2024
44 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 subtypeMolecular 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 trials
2022
Germline variants associated with toxicity to immune checkpoint blockade
Groha S, Alaiwi S, Xu W, Naranbhai V, Nassar A, Bakouny Z, El Zarif T, Saliby R, Wan G, Rajeh A, Adib E, Nuzzo P, Schmidt A, Labaki C, Ricciuti B, Alessi J, Braun D, Shukla S, Keenan T, Van Allen E, Awad M, Manos M, Rahma O, Zubiri L, Villani A, Fairfax B, Hammer C, Khan Z, Reynolds K, Semenov Y, Schrag D, Kehl K, Freedman M, Choueiri T, Gusev A. Germline variants associated with toxicity to immune checkpoint blockade. Nature Medicine 2022, 28: 2584-2591. PMID: 36526723, PMCID: PMC10958775, DOI: 10.1038/s41591-022-02094-6.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsImmune checkpoint inhibitorsGrade immune-related adverse eventsGermline variantsICI initiationCheckpoint inhibitorsAdverse eventsCheckpoint blockadeImproved survivalDiscovery cohortLymphocyte homeostasisSignificant associationCancer typesIL7Remarkable responsePatientsCritical regulatorGenome-wide significant associationAssociationWide association studyIndependent studiesAssociation studiesBlockadeCohortVariantsSpatially mapping T cell receptors and transcriptomes
Liu S, Iorgulescu J, Li S, Barrera-Lopez I, Borji M, Shanmugam V, Morriss J, Garcia Z, Murray E, Braun D, Livak K, Wu C, Chen F. Spatially mapping T cell receptors and transcriptomes. The Journal Of Immunology 2022, 208: 172.01-172.01. DOI: 10.4049/jimmunol.208.supp.172.01.Peer-Reviewed Original ResearchT cell clonotypesT cell receptorCell clonotypesGerminal centersTCR repertoireT cellsAntigen-specific immune responsesHuman reactive lymph nodesDistinct TCR repertoireImmune checkpoint blockadeReactive lymph nodesRenal cell carcinomaAbstract T cellsT cell maturationT cell developmentCheckpoint blockadeLymph nodesCell carcinomaImmune microenvironmentImmune responseClonotypesMouse spleenCell maturationCell receptorReceptors
2016
Genomic Approaches to Understanding Response and Resistance to Immunotherapy
Braun D, Burke K, Van Allen E. Genomic Approaches to Understanding Response and Resistance to Immunotherapy. Clinical Cancer Research 2016, 22: 5642-5650. PMID: 27698000, PMCID: PMC5135569, DOI: 10.1158/1078-0432.ccr-16-0066.Peer-Reviewed Original ResearchConceptsSubset of patientsCheckpoint blockadeSuch therapyImmune checkpoint blockadeImmune-based therapiesNumber of patientsLow intratumoral heterogeneityDurable responsesImmune checkpointsAdvanced cancerLoss of PTENNeoantigen loadPoint of careCertain patientsMechanisms of resistanceResistant tumorsPatientsTherapyTumor progressionImmunotherapyAppropriate functional studiesIntratumoral heterogeneityLimited responseBlockadePositive correlates