2025
Polymyalgia Rheumatica-Like Syndrome Post Immune Checkpoint Inhibitor Therapy
Lu H, Bowman S, Linda Bobby N, Kim S, Msaouel P, Tayar J. Polymyalgia Rheumatica-Like Syndrome Post Immune Checkpoint Inhibitor Therapy. 2025, 433-438. DOI: 10.1007/978-3-031-83533-9_54.Peer-Reviewed Original ResearchMetastatic clear cell renal cell carcinomaClear cell renal cell carcinomaPMR-like syndromeProximal muscle painCell renal cell carcinomaRenal cell carcinomaMaintenance prednisoneTapering prednisoneClinical remissionCell carcinomaMuscle painInflammation markersPrednisoneSarilumabIpilimumabNivolumabRemissionCarcinomaPainSyndromeInflammationNeckImmunogenomic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma
Jammihal T, Saliby R, Labaki C, Soulati H, Gallegos J, Peris A, McCurry D, Yu C, Shah V, Poduval D, El Zarif T, El Ahmar N, Laimon Y, Eid M, Sheshdeh A, Krajewski K, Büttner F, Schwab M, Heng D, Casellas R, Rai K, Zacharias Millward N, Msaouel P, Karam J, Signoretti S, Van Allen E, Choueiri T, Braun D, Shukla S. Immunogenomic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma. Nature Cancer 2025, 6: 372-384. PMID: 39789182, PMCID: PMC12121501, DOI: 10.1038/s43018-024-00896-w.Peer-Reviewed Original ResearchConceptsTertiary lymphoid structuresVascular endothelial growth factorRenal cell carcinomaCell carcinomaCytotoxic T-lymphocyte-associated protein 4 inhibitorsResponse to immune checkpoint inhibitionExceptional responseMetastatic clear cell renal cell carcinomaStandard-of-care immunotherapiesTertiary lymphoid structure formationCytotoxic T cell responsesClear cell renal cell carcinomaIO-based treatmentsTreatment-naive personsImmune checkpoint inhibitionImmune checkpoint inhibitorsCell renal cell carcinomaT cell responsesT-cell-directedEndothelial growth factorCell death proteinAntitumor immunityCheckpoint inhibitionCheckpoint inhibitorsNeoantigen load
2024
Expression of the receptor tyrosine kinase AXL and clinical outcomes to cabozantinib and everolimus in patients with metastatic renal cell carcinoma enrolled in the METEOR trial.
Nabil Laimon Y, Paul M, Ghandour F, El Ahmar N, Matar S, Denize T, Bagheri Sheshdeh A, Savla V, Mohanna R, Sun M, Saliby R, Saad E, Machaalani M, Braun D, Aftab D, Xie W, CHOUEIRI T, Signoretti S. Expression of the receptor tyrosine kinase AXL and clinical outcomes to cabozantinib and everolimus in patients with metastatic renal cell carcinoma enrolled in the METEOR trial. Journal Of Clinical Oncology 2024, 42: 4543-4543. DOI: 10.1200/jco.2024.42.16_suppl.4543.Peer-Reviewed Original ResearchProgression-free survivalAssociated with progression-free survivalReceptor tyrosine kinase AXLTyrosine kinase inhibitorsRenal cell carcinomaImmune cellsMETEOR trialTyrosine kinase AXLAxl expressionTumor cellsCell carcinomaAssociated with shorter progression-free survivalMetastatic clear cell renal cell carcinomaAnti-PD-1 therapyLevels of AXL expressionMetastatic renal cell carcinomaMultitargeted tyrosine kinase inhibitorPresence of bone metastasesShorter progression-free survivalClear cell renal cell carcinomaIMDC risk groupsPretreatment tumor tissueVEGFR-TKI treatmentCell renal cell carcinomaDouble immunohistochemistry stainingAdvanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587).
Serzan M, Jegede O, Alter R, Bilen M, Braun D, Einstein D, Haas N, Herchenhorn D, King J, Runcie K, Sosman J, Sternberg C, Yang Y, Signoretti S, CHOUEIRI T, Atkins M. Advanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587). Journal Of Clinical Oncology 2024, 42: tps4614-tps4614. DOI: 10.1200/jco.2024.42.16_suppl.tps4614.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsArm BArm APrimary endpointRate of immune-related adverse eventsMetastatic clear cell renal cell carcinomaImmune-related adverse eventsMolecular predictors of responseVEGF receptor tyrosine kinase inhibitorReceptor tyrosine kinase inhibitorsEnhance T cell primingOne-sided significance levelClear cell renal cell carcinomaAnti-PD1 inhibitorsIMDC risk groupsTreatment free intervalProgression-free survivalT cell primingTreatment-free survivalCell renal cell carcinomaSubpopulations of TregsFirst-line treatmentRenal cell carcinomaPredictors of responseAssociated with increased presenceIntratumoral T-cell infiltration and response to nivolumab plus ipilimumab in patients with metastatic clear cell renal cell carcinoma from the CheckMate-214 trial.
Matar S, Jegede O, Denize T, Ghandour F, Nabil Laimon Y, El Ahmar N, Bagheri Sheshdeh A, Savla V, Mohanna R, Catalano P, Braun D, Sun M, Gupta S, Vemula S, Freeman G, Motzer R, Atkins M, McDermott D, CHOUEIRI T, Signoretti S. Intratumoral T-cell infiltration and response to nivolumab plus ipilimumab in patients with metastatic clear cell renal cell carcinoma from the CheckMate-214 trial. Journal Of Clinical Oncology 2024, 42: 4536-4536. DOI: 10.1200/jco.2024.42.16_suppl.4536.Peer-Reviewed Original ResearchProgression-free survivalAssociated with progression-free survivalMultiplex immunofluorescenceClinical trialsClinical outcomesMetastatic clear cell renal cell carcinomaIntratumoral T cell infiltrationTreated with nivolumab monotherapyMetastatic clear cell RCCClear cell renal cell carcinomaResponse to nivolumabT cell infiltrationCell renal cell carcinomaPoor-risk patientsRenal cell carcinomaClear cell RCCFormalin Fixed ParaffinContinuous variablesNivolumab monotherapyCox proportional hazardsAntigen-experiencedCell RCCCell carcinomaLogistic regression modelsPositive associationAdvanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587).
Serzan M, Jegede O, Bilen M, Braun D, Einstein D, Haas N, Hammers H, King J, Runcie K, Sosman J, Sternberg C, Yang Y, Choueiri T, Signoretti S, Atkins M. Advanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587). Journal Of Clinical Oncology 2024, 42: tps492-tps492. DOI: 10.1200/jco.2024.42.4_suppl.tps492.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsArm BArm APrimary endpointRate of immune-related adverse eventsMetastatic clear cell renal cell carcinomaImmune-related adverse eventsMolecular predictors of responseVEGF receptor tyrosine kinase inhibitorReceptor tyrosine kinase inhibitorsEnhance T cell primingOne-sided significance levelClear cell renal cell carcinomaAnti-PD1 inhibitorsIMDC risk groupsTreatment free intervalProgression-free survivalT cell primingTreatment-free survivalCell renal cell carcinomaSubpopulations of TregsFirst-line treatmentRenal cell carcinomaPredictors of responseAnti-tumor activityPD-1 Expression on Intratumoral Regulatory T Cells Is Associated with Lack of Benefit from Anti-PD-1 Therapy in Metastatic Clear-Cell Renal Cell Carcinoma Patients.
Denize T, Jegede O, Matar S, El Ahmar N, West D, Walton E, Bagheri A, Savla V, Nabil Laimon Y, Gupta S, Vemula S, Braun D, Burke K, Catalano P, Freeman G, Motzer R, Atkins M, McDermott D, Sharpe A, Choueiri T, Signoretti S. PD-1 Expression on Intratumoral Regulatory T Cells Is Associated with Lack of Benefit from Anti-PD-1 Therapy in Metastatic Clear-Cell Renal Cell Carcinoma Patients. Clinical Cancer Research 2024, 30: 803-813. PMID: 38060202, PMCID: PMC10922154, DOI: 10.1158/1078-0432.ccr-23-2274.Peer-Reviewed Original ResearchPD-1 expressionObjective response rateProgression-free survivalLow objective response rateShorter progression-free survivalPD-1 blockadeRegulatory T cellsShorter overall survivalOverall survivalPD-1Nivolumab armT cellsMetastatic clear-cell renal cell carcinoma patientsMetastatic clear cell renal cell carcinomaAnti-PD-1 therapyIntratumoral regulatory T cellsClear cell renal cell carcinoma patientsRenal cell carcinoma patientsClear cell renal cell carcinomaPD-1 inhibitorsPD-1 inhibitionCell carcinoma patientsCell renal cell carcinomaExpression of CD8Tumor-infiltrating Tregs
2023
Genomic and Transcriptomic Characteristics of Tumors of Patients with Metastatic Clear Cell Renal Cell Carcinoma Clinically Benefiting from First-Line Treatment with Ipilimumab Plus Nivolumab
Tripathi N, Meza L, Sayegh N, Govindarajan A, Byron S, Zhang J, Chigarira B, Jo Y, Zengin Z, Li H, Gebrael G, Desai A, Agarwal N, Swami U, Maughan B, Pal S. Genomic and Transcriptomic Characteristics of Tumors of Patients with Metastatic Clear Cell Renal Cell Carcinoma Clinically Benefiting from First-Line Treatment with Ipilimumab Plus Nivolumab. Kidney Cancer 2023, 7: 137-145. DOI: 10.3233/kca-230011.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaClear cell metastatic renal cell carcinomaClinical benefit groupRenal cell carcinomaClinical benefitNivolumab therapyCell carcinomaPoor-risk metastatic renal cell carcinomaMetastatic clear cell renal cell carcinomaBenefit groupClear cell renal cell carcinomaFirst-line ipilimumabIMDC risk scoresFirst-line treatmentCell renal cell carcinomaAlteration frequencyChi-square testMRCC patientsStable diseaseComplete responsePartial responseSystemic therapyLine treatmentInflammatory pathwaysTumor-specific gene expressionCD70 is Consistently Expressed in Primary and Metastatic Clear Cell Renal Cell Carcinoma
Huang R, Chen Z, Kroeger N, Pantuck A, Said J, Kluger H, Shuch B, Ye H. CD70 is Consistently Expressed in Primary and Metastatic Clear Cell Renal Cell Carcinoma. Clinical Genitourinary Cancer 2023, 22: 347-353. PMID: 38195301, DOI: 10.1016/j.clgc.2023.12.003.Peer-Reviewed Original ResearchRenal cell carcinomaClear cell renal cell carcinomaCell renal cell carcinomaMetastatic clear cell renal cell carcinomaMetastatic renal cell carcinomaCell carcinomaClear cell carcinomaCD70 expressionMetastatic tumorsRenal tumorsTherapeutic targetAdvanced renal cell carcinomaMetastatic clear cell carcinomaCancer-specific survivalPapillary renal cell carcinomaExpression of CD70Normal renal parenchymaPrimary renal tumorsPrimary tumor tissuesPromising therapeutic targetPotential therapeutic targetHypoxia pathway proteinsHypoxia-inducible factorSarcomatoid differentiationNormal human tissuesEmerging 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 outcomesTherapyBiomarkersRegimensPatientsCarcinomaMccRCCResponseA phase 2 study of the WEE1 inhibitor AZD1775 in SETD2-deficient advanced solid tumor malignancies.
Maldonado E, Rathmell W, Shapiro G, Rodon Ahnert J, Mahalingam D, Trikalinos N, Rezazadeh A, Adorno Febles V, Parikh M, Boerner S, Krings G, Takebe N, LoRusso P, Aggarwal R. A phase 2 study of the WEE1 inhibitor AZD1775 in SETD2-deficient advanced solid tumor malignancies. Journal Of Clinical Oncology 2023, 41: 3104-3104. DOI: 10.1200/jco.2023.41.16_suppl.3104.Peer-Reviewed Original ResearchClear cell renal cell carcinomaSolid tumor malignanciesClinical benefit rateObjective response rateDuration of responseTumor malignancyEvaluable ptsStable diseaseObjective responseAdverse eventsTumor regressionMetastatic clear cell renal cell carcinomaAdvanced solid tumor malignanciesMetastatic solid tumor malignanciesCommon adverse eventsDurable stable diseaseECOG PS 0RECIST 1.1 criteriaSubset of ptsPhase 2 studyCohort of patientsCell renal cell carcinomaNext-generation sequencing panelBest overall responseRenal cell carcinoma
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 ResearchConceptsTC 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
Molecular correlates of response to nivolumab at baseline and on treatment in patients with RCC
Ross-Macdonald P, Walsh AM, Chasalow SD, Ammar R, Papillon-Cavanagh S, Szabo PM, Choueiri TK, Sznol M, Wind-Rotolo M. Molecular correlates of response to nivolumab at baseline and on treatment in patients with RCC. Journal For ImmunoTherapy Of Cancer 2021, 9: e001506. PMID: 33658305, PMCID: PMC7931766, DOI: 10.1136/jitc-2020-001506.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, TumorCarcinoma, Renal CellCD4 AntigensCD8 AntigensCytokinesDrug Resistance, NeoplasmHumansImmune Checkpoint InhibitorsKidney NeoplasmsLymphocytes, Tumor-InfiltratingMutationNivolumabProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-CellT-LymphocytesTime FactorsTreatment OutcomeConceptsClear cell renal cell carcinomaMetastatic clear cell renal cell carcinomaT cell infiltrationNivolumab responseExact testDeath ligand 1 (PD-L1) statusFirst-line treatment decisionsT-cell receptor clonalitySerum cytokine assaysImmune checkpoint inhibitorsNon-responding patientsDeath-1 receptorCell renal cell carcinomaSubset of patientsRenal cell carcinomaFisher's exact testWnt/β-cateninLogistic regression modelsRank sum testCD8 statusCheckpoint inhibitorsIndex lesionPatient selectionTCR clonalityCell carcinoma
2020
Activity of cabozantinib after immune checkpoint blockade in metastatic clear-cell renal cell carcinoma
McGregor BA, Lalani AA, Xie W, Steinharter JA, Bakouny Z, Martini DJ, Fleischer JH, Abou-Alaiwi S, Nassar A, Nuzzo PV, Kaymakcalan MD, Braun DA, Wei XX, Harshman LC, Bilen MA, Choueiri TK. Activity of cabozantinib after immune checkpoint blockade in metastatic clear-cell renal cell carcinoma. European Journal Of Cancer 2020, 135: 203-210. PMID: 32599410, DOI: 10.1016/j.ejca.2020.05.009.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAngiogenesis InhibitorsAnilidesAntineoplastic Combined Chemotherapy ProtocolsBostonCarcinoma, Renal CellFemaleGeorgiaHumansImmune Checkpoint InhibitorsKidney NeoplasmsMaleMiddle AgedProtein Kinase InhibitorsPyridinesRetrospective StudiesTime FactorsTreatment OutcomeConceptsMetastatic clear cell renal cell carcinomaImmune checkpoint blockadeClear cell renal cell carcinomaActivity of cabozantinibRenal cell carcinomaOverall survivalTreatment failureCheckpoint blockadeCell carcinomaDose reductionAnti-PD-1/PD-L1International Metastatic RCC Database ConsortiumVascular endothelial growth factor inhibitorsSubsequent-line treatmentUse of cabozantinibIntermediate-risk groupMedian overall survivalMedian TTFHalf of patientsNew safety signalsPalmar-plantar erythrodysesthesiaPrimary progressive diseaseGrowth factor inhibitorsOverall response rateMost common reasons
2015
MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors
Shuch B, Falbo R, Parisi F, Adeniran A, Kluger Y, Kluger HM, Jilaveanu LB. MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors. BioMed Research International 2015, 2015: 192406. PMID: 26448928, PMCID: PMC4584049, DOI: 10.1155/2015/192406.Peer-Reviewed Original ResearchConceptsClear cell renal cell carcinomaCell renal cell carcinomaMetastatic sitesRenal cell carcinomaMET expressionCell carcinomaPredictive biomarkersPrimary tumorMetastatic clear cell renal cell carcinomaMetastatic kidney cancerAppropriate patient selectionDistant metastatic sitesPatient selectionMetastatic tissuesKidney cancerMET pathwayTissue microarrayBiomarker assessmentNumber of casesPrimary siteModerate concordancePathway inhibitorTumorsDistant tissuesNephrectomy
2009
Prognostic and predictive values of carbonic anhydrase IX (CAIX) and pathologic features in patients with metastatic clear cell renal cell carcinoma receiving targeted therapy
Choueiri T, Regan M, Oh W, Clement J, Amato A, McDermott D, Cho D, Atkins M, Signoretti S. Prognostic and predictive values of carbonic anhydrase IX (CAIX) and pathologic features in patients with metastatic clear cell renal cell carcinoma receiving targeted therapy. Journal Of Clinical Oncology 2009, 27: e16067-e16067. DOI: 10.1200/jco.2009.27.15_suppl.e16067.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaVEGF-targeted therapyCarbonic anhydrase IXCarbonic anhydrase IX expressionRenal cell carcinomaTumor shrinkageCell carcinomaCAIX expressionHistological featuresAssociated with greater tumor shrinkageMetastatic clear cell renal cell carcinomaClear cell renal cell carcinomaResponse to sorafenib treatmentSunitinib-treated patientsResponse to sunitinibSorafenib-treated patientsTreated with immunotherapyCell renal cell carcinomaClear cell componentCell histologySorafenib treatmentPredictive biomarkersPrognostic valueTargeted therapyClinical benefit
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