2024
Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma
Schoenfeld D, Djureinovic D, Su D, Zhang L, Lu B, Kamga L, Mann J, Huck J, Hurwitz M, Braun D, Jilaveanu L, Ring A, Kluger H. Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma. JCI Insight 2024 PMID: 39561007, DOI: 10.1172/jci.insight.184545.Peer-Reviewed Original ResearchAnti-CTLA-4Renal cell carcinomaIL-18IL-18BPCell carcinomaTumor microenvironmentTumor typesPatients treated with immune checkpoint inhibitorsRegulatory T cell levelsAnti-PD-1 treatmentCD8+ T cellsAnti-PD-1Immune checkpoint inhibitorsCell renal cell carcinomaNon-responder patientsMyeloid cell populationsT cell levelsCytokine interleukin-18Anti-cancer efficacySecreted binding proteinCheckpoint inhibitorsResponding patientsPreclinical modelsT cellsMurine modelTIGIT 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 carcinoma
2023
Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors
Kluger H, Barrett J, Gainor J, Hamid O, Hurwitz M, LaVallee T, Moss R, Zappasodi R, Sullivan R, Tawbi H, Sharon E. Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors. Journal For ImmunoTherapy Of Cancer 2023, 11: e005921. PMID: 36918224, PMCID: PMC10016305, DOI: 10.1136/jitc-2022-005921.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsCheckpoint inhibitorsAnti-PD-1 immune checkpoint inhibitorTrial designConsensus definitionConsensus clinical definitionExtended disease controlNew combination regimensImmunotherapy of cancerStandard of careLong-term survivalClinical trial designICI combinationsInitial immunotherapyMetastatic settingTreatment discontinuationDurable responsesTreatment landscapeCombination regimensMechanisms of resistancePerioperative settingPrimary resistanceClinical definitionDefinition of resistanceImmunotherapyEvolution of systemic therapy from 2015 to 2019 for older patients in the United States with metastatic renal cell carcinoma.
Chow R, Long J, Hassan S, Wheeler S, Spees L, Leapman M, Hurwitz M, McManus H, Gross C, Dinan M. Evolution of systemic therapy from 2015 to 2019 for older patients in the United States with metastatic renal cell carcinoma. Journal Of Clinical Oncology 2023, 41: 610-610. DOI: 10.1200/jco.2023.41.6_suppl.610.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaImmune checkpoint inhibitorsOral anti-cancer agentsNon-Hispanic white patientsSystemic therapyRenal cell carcinomaNHW patientsWhite patientsCell carcinomaMedicare beneficiariesService Medicare Parts ARetrospective cohort studyOverall treatment rateMedicare Part AIO therapyMRCC therapyAnti-cancer agentsCheckpoint inhibitorsCohort studyOlder patientsRandomized trialsSurvival improvementFirst therapyStudy criteriaTreatment receiptOutcomes 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 ResearchConceptsMetastatic 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
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
2017
Effect of NKTR-214 on the number and activity of CD8+ tumor infiltrating lymphocytes in patients with advanced renal cell carcinoma.
Hurwitz M, Diab A, Bernatchez C, Haymaker C, Kluger H, Tetzlaff M, Gergel I, Tagliaferri M, Imperiale M, Aung S, Hoch U, Zalevsky J, Hwu P, Sznol M, Tannir N. Effect of NKTR-214 on the number and activity of CD8+ tumor infiltrating lymphocytes in patients with advanced renal cell carcinoma. Journal Of Clinical Oncology 2017, 35: 454-454. DOI: 10.1200/jco.2017.35.6_suppl.454.Peer-Reviewed Original ResearchNKTR-214T cellsTumor microenvironmentIL-2 receptor pathwayAnti-PD-1 blockadeAdvanced renal cell carcinomaImmune-related AEPatient experienced DLTPrior TKI treatmentImmune checkpoint inhibitorsT-cell receptor diversityAdvanced solid tumorsPD-1 expressionT-cell infiltratesActivity of CD8Effector T cellsFavorable safety profileRenal cell carcinomaAnti-tumor activityBaseline CD8Experienced DLTsLow TILsRECIST 1.1Checkpoint inhibitorsEffector CD8