2025
Presence of tertiary lymphoid structures and exhausted tissue-resident T cells determines clinical response to PD-1 blockade in renal cell carcinoma.
Hugaboom M, Wirth L, Street K, Ruthen N, Jegede O, Schindler N, Shah V, Zaemes J, El Ahmar N, Matar S, Savla V, Choueiri T, Denize T, West D, McDermott D, Plimack E, Sosman J, Haas N, Stein M, Alter R, Bilen M, Hurwitz M, Hammers H, Signoretti S, Atkins M, Wu C, Braun D. Presence of tertiary lymphoid structures and exhausted tissue-resident T cells determines clinical response to PD-1 blockade in renal cell carcinoma. Cancer Discovery 2025, of1-of21. PMID: 39992403, DOI: 10.1158/2159-8290.cd-24-0991.Peer-Reviewed Original ResearchTertiary lymphoid structuresRenal cell carcinomaCD8+ T cellsAnti-PD1 monotherapyImmune checkpoint inhibitorsT cellsCell carcinomaLymphoid structuresClinical outcomesClinical response to PD-1 blockadeTreatment of advanced renal cell carcinomaResponse to PD-1 blockadePresence of tertiary lymphoid structuresAdvanced renal cell carcinomaTissue-resident T cellsPD-1 blockadePhase II clinical trialPD-1 pathwayCheckpoint inhibitorsICI resistancePD-1Responding patientsTumor microenvironmentTherapeutic responseTissue-residentProgressive natural killer cell dysfunction in advanced-stage clear-cell renal cell carcinoma and association with clinical outcomes
Xu W, Birch G, Meliki A, Moritz V, Bharadwaj M, Schindler N, Labaki C, Saliby R, Dinh K, Horst J, Sun M, Kashima S, Hugaboom M, Dighe A, Machaalani M, Lee G, Hurwitz M, McGregor B, Hirsch M, Shukla S, McDermott D, Signoretti S, Romee R, Choueiri T, Braun D. Progressive natural killer cell dysfunction in advanced-stage clear-cell renal cell carcinoma and association with clinical outcomes. ESMO Open 2025, 10: 104105. PMID: 39813824, PMCID: PMC11783098, DOI: 10.1016/j.esmoop.2024.104105.Peer-Reviewed Original ResearchConceptsClear-cell renal cell carcinomaAdvanced clear-cell renal cell carcinomaNK cell phenotypeNK cell functionNK cellsRenal cell carcinomaClinical outcomesCell carcinomaCell phenotypeRestoration of NK cell functionNormal kidneyNatural killer (NK) cellsMarkers of tissue residencyNatural killer cell dysfunctionAssociated with worse overall survivalClear-cell renal cell carcinoma patientsLocalized clear-cell renal cell carcinomaTumor-infiltrating NK cellsAnalyzed single-cell RNA sequencing dataAssociated with worse survivalExpression of cytotoxic genesPaired normal kidneyLocal tumor extensionNK cell subsetsPrimary tumor specimens
2020
Phase II study of nivolumab and salvage nivolumab + ipilimumab in treatment-naïve patients (pts) with advanced renal cell carcinoma (RCC) (HCRN GU16-260).
Atkins M, Jegede O, Haas N, McDermott D, Bilen M, Drake C, Sosman J, Alter R, Plimack E, Rini B, Hurwitz M, Peace D, Signoretti S, Wu C, Catalano P, Hammers H. Phase II study of nivolumab and salvage nivolumab + ipilimumab in treatment-naïve patients (pts) with advanced renal cell carcinoma (RCC) (HCRN GU16-260). Journal Of Clinical Oncology 2020, 38: 5006-5006. DOI: 10.1200/jco.2020.38.15_suppl.5006.Peer-Reviewed Original ResearchRenal cell carcinomaProgressive diseaseStable diseaseGrade 3Sarcomatoid histologyPoor-risk renal-cell carcinomaAdvanced renal cell carcinomaMedian age 65Symptomatic progressive diseaseTreatment-related AEsTreatment-naïve patientsPhase II studyWk of treatmentEligible ptsImDC groupIpilimumab combinationMedian DoRMedian PFSSalvage therapyRespiratory failureSalvage treatmentII studyClinical outcomesMetastatic lesionsCell carcinoma
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