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 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
2017
A phase 1/2 study of a novel IL-2 cytokine, NKTR-214, and nivolumab in patients with select locally advanced or metastatic solid tumors.
Diab A, Tannir N, Bernatchez C, Haymaker C, Bentebibel S, Curti B, Wong M, Gergel I, Tagliaferri M, Zalevsky J, Hoch U, Aung S, Imperiale M, Cho D, Tykodi S, Puzanov I, Kluger H, Hurwitz M, Hwu P, Sznol M. A phase 1/2 study of a novel IL-2 cytokine, NKTR-214, and nivolumab in patients with select locally advanced or metastatic solid tumors. Journal Of Clinical Oncology 2017, 35: e14040-e14040. DOI: 10.1200/jco.2017.35.15_suppl.e14040.Peer-Reviewed Original ResearchNKTR-214Phase 1/2 studyT cellsIL-2 receptor pathwayTumor immune cell infiltratesTumor microenvironmentNivolumab combination therapyDose limiting toxicitiesImmune cell infiltratesUnconfirmed complete responseMetastatic solid tumorsWeeks of treatmentFavorable safety profileIL-2 pathwayIL-2 cytokineT-cell clonalityBiomarker dataTumor response dataImmunotherapy-naïveMonotherapy trialsQ3w scheduleRECIST 1.1Checkpoint inhibitorsEffector CD8Adverse eventsEffect 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
2016
Changes in T cell immunity in patients with metastatic castration resistant prostate treated with Radium-223 treatment.
Kim J, Kang Y, Shin M, Deshpande H, Hurwitz M, Roberts J, Cardinale J, Narayana A, Kang I, Petrylak D. Changes in T cell immunity in patients with metastatic castration resistant prostate treated with Radium-223 treatment. Journal Of Clinical Oncology 2016, 34: 295-295. DOI: 10.1200/jco.2016.34.2_suppl.295.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerPeripheral blood mononuclear cellsT cell immunityT cellsCell immunityOsseous metastasesMetastatic castration-resistant prostateCastration-resistant prostate cancerIL-7 receptor alpha chainRadium-223 treatmentEffector memory CD8PD-1 expressionEffector T cellsDeath protein 1Resistant prostate cancerCastration-resistant prostateBlood mononuclear cellsFollowing time pointsCocktail of antibodiesHost immune systemReceptor alpha chainCalcium mimeticEligible patientsEM CD8Median PSA