164 IRRADIATION OF RENAL CELL CARCINOMA CELL LINES INCREASES THEIR IMMUNOGENICITY

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research (I)1 Apr 2013164 IRRADIATION OF RENAL CELL CARCINOMA CELL LINES INCREASES THEIR IMMUNOGENICITY Gregory Janda, Scott Abrams, Mohammad Habiby, Michelle Romano, Jan Hoffmeyer, Graham Warren, and Thomas Schwaab Gregory JandaGregory Janda Buffalo, NY More articles by this author , Scott AbramsScott Abrams Buffalo, NY More articles by this author , Mohammad HabibyMohammad Habiby Buffalo, NY More articles by this author , Michelle RomanoMichelle Romano Buffalo, NY More articles by this author , Jan HoffmeyerJan Hoffmeyer Buffalo, NY More articles by this author , Graham WarrenGraham Warren 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.2013.02.1544AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cellular vaccine therapy in Renal Cell Carcinoma (RCC) has shown disappointing clinical and immunologic results. Poor immunogenicity of tumor associated antigens (TAAs) and their restricted expression may account for a lack of antigen-specific T cell responses. Irradiation induces TAA expression and enhances the immunogenicity of tumor cells. We investigated the influence of radiation on the immunogenicity of RCC tumor cells. METHODS Six (ACHN, 786-0, 769-P, Caki-1, A-498, A-704) commercially available RCC cell lines were cultured and subsequently exposed to 0, 12 or 16 Gy of ionizing radiation. Alive cells and supernatant were isolated at 2, 24 and 48 hours after irradiation. The TAA expression (CA9, 5T4, MUC-1, NY-ESO-1, HSP70) was assessed using flow cytometry. Expression relative to control (ERC) was calculated. Cytokine analysis was performed using a 9-plex Luminex human cytokine assay and reported as the mean concentration of all cell lines. RESULTS CA9, 5T4 and NY-ESO-1 demonstrated a marked increase in expression in 4 of 6 cell lines while MUC-1 and HSP70 had increased expression in all cell lines after irradiation. The range and mean ERC across all six cell lines at 48 hours after irradiation with 16 Gy are tabulated below. Il-2, Il-6, IFN-gamma and Il-4 increased in irradiated cells with peak concentrations vs. control of: 0.55 vs. 0.47, 1631 vs. 1358, 10.06 vs. 7.61, 1.07 vs. 0.77 pg/ml, respectively. CONCLUSIONS Irradiation of RCC cell lines increased TAA expression in the majority of cell lines. Immunomodulatory cytokines were induced with radiation. These data suggest that RCC tumor irradiation may provide a novel means to increase the immunogenicity and subsequent efficacy of RCC-targeted immunotherapy. TAA ERC Range Mean ERC CA9 0.35 - 7.17 2.95 5T4 0.63 - 5.64 2.03 NY-ESO-1 0.65 - 5.85 2.27 MUC-1 0.50 - 5.02 2.64 HSP70 1.41 - 4.41 2.97 © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e67-e68 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Gregory Janda Buffalo, NY More articles by this author Scott Abrams Buffalo, NY More articles by this author Mohammad Habiby Buffalo, NY More articles by this author Michelle Romano Buffalo, NY More articles by this author Jan Hoffmeyer Buffalo, NY More articles by this author Graham Warren Buffalo, NY More articles by this author Thomas Schwaab Buffalo, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...