You have accessJournal of UrologyKidney Cancer: Basic Research III1 Apr 2012440 GENOMIC PROFILING OF MONOCYTES IN PATIENT WITH METASTATIC RENAL CELL CARCINOMA (RCC) TREATED WITH IMMUNOTHERAPY Matthew Farren, Jeremy Wright, Jeff Miecznikowski, Lee Kang, Kelvin Lee, Marc Ernstoff, Scott Abrams, and Thomas Schwaab Matthew FarrenMatthew Farren Buffalo, NY More articles by this author , Jeremy WrightJeremy Wright Buffalo, NY More articles by this author , Jeff MiecznikowskiJeff Miecznikowski Buffalo, NY More articles by this author , Lee KangLee Kang Buffalo, NY More articles by this author , Kelvin LeeKelvin Lee Buffalo, NY More articles by this author , Marc ErnstoffMarc Ernstoff Lebanon, NH More articles by this author , Scott AbramsScott Abrams Buffalo, NY More articles by this author , and Thomas SchwaabThomas Schwaab Buffalo, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.507AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Previous studies have demonstrated significant differences of immune cell populations in patients with RCC. We demonstrated previously a prognostic genomic profile in lymphocytes of RCC patients. In this study, we set out to investigate the genomic profile of peripheral blood monocytes in patients with metastatic RCC treated with immunotherapy. METHODS Metastatic RCC patients were enrolled in an IRB-approved Phase II trial treating patients with an autologous tumor-pulsed Dendritic Cell (DC) vaccine combined with high-dose IL-2. CD14+ monocytes were isolated via leukapheresis/ clinimax at different time points for DC vaccine preparation. mRNA was isolated from purified monocytes in the standard fashion and a cDNA microarray was created using the Affimetrix gene chip system. For biostatistical analysis, patients were divided into pre- and post-treatment, responders (complete + partial response) and non-responders (stable disease). Healthy age-matched donors were used as controls. KEGG pathway analysis was utilized to analyze genes of interest. RESULTS Of the 18 patients enrolled in the trial, samples were available for a total of 13 patients (7 responders, 6 non-responders) and 4 healthy donors. When healthy age-matched donors were compared to RCC patients, a total of 86 genes were found to be differently expressed (p<0.001). In KEGG pathway analysis, immunotherapy resulted in down-regulation of 3 and up-regulation of 4 gene pathways. In KEGG pathway analysis, the ”arginine and proline metabolism” pathway was predictive for treatment response (p<0.001). The same pathway was differentially expressed between healthy donors, pre- and post-treatment groups (p<0.001). Similary, the ”Glutathione metabolism”, ”nitrogen metabolism”, and ”Jak-STAT signaling pathway” were differentially expressed between healthy donors when compared to pre- and post-treatment samples (p<0.001). CONCLUSIONS In conclusion, we show distinct genomic differences in monocytes between healthy donors and patients with metastatic RCC. In addition, we demonstrate genomic differences between responders and non-responders. Finally, immunotherapy resulted in significant changes in the gene profile of monocytes. In particular, the implicated arginine/proline, glutathione and nitrogen metabolism pathways have been demonstrated to have significant impact on monocyte-mediated anti-tumor immune responses and may play a significant role for patients undergoing immunotherapy. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e180 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew Farren Buffalo, NY More articles by this author Jeremy Wright Buffalo, NY More articles by this author Jeff Miecznikowski Buffalo, NY More articles by this author Lee Kang Buffalo, NY More articles by this author Kelvin Lee Buffalo, NY More articles by this author Marc Ernstoff Lebanon, NH More articles by this author Scott Abrams Buffalo, NY More articles by this author Thomas Schwaab Buffalo, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...