You have accessJournal of UrologyKidney Cancer: Basic Research1 Apr 2011383 RADIOFREQUENCY ABLATION COMBINED WITH INTERLEUKIN-2 PREVENTS METASTASIS FORMATION IN MOUSE RENAL CELL CARCINOMA Stephanie G.C. Kroeze, Maarten W. Nijkamp, Jeanine M.L. Roodhart, Gijsbert C. de Gast, J.L.H. Ruud Bosch, and Judith J.M. Jans Stephanie G.C. KroezeStephanie G.C. Kroeze Utrecht, Netherlands More articles by this author , Maarten W. NijkampMaarten W. Nijkamp Utrecht, Netherlands More articles by this author , Jeanine M.L. RoodhartJeanine M.L. Roodhart Utrecht, Netherlands More articles by this author , Gijsbert C. de GastGijsbert C. de Gast Amsterdam, Netherlands More articles by this author , J.L.H. Ruud BoschJ.L.H. Ruud Bosch Utrecht, Netherlands More articles by this author , and Judith J.M. JansJudith J.M. Jans Utrecht, Netherlands More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.471AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Approximately 50% of patients diagnosed with renal cell carcinoma (RCC) develop metastases. For these patients survival rates are poor. In addition to targeted therapy, immune based therapies have gained renewed interest. Radiofrequency ablation (RFA) induces a tumorspecific immune response in colorectal metastases and melanomas that can be enhanced with immunostimulatory agents. This study aimed to determine the antitumor effect of RFA combined with Interleukin-2 (IL2) on RCC, using a preclinical mouse model. Importantly, the presented in situ activation of an antitumor response by RFA holds numerous advantages over currently available (immune) therapies. METHODS Orthotopically transplanted renal tumors (n>8 mice/group) were treated with RFA, high-dose IL2 or a combination. Lung metastases were induced by i.v. injection of Renca cells. 21 days after RFA/IL2 treatment macroscopic lung metastases were counted. CD8+ T and NK cells derived from spleens (n=3/group) 9 days following treatment were measured by magnetic bead sorting. For tumor-specific cytotoxicity Renca cells were mixed with NK and CD8+ T cells and analysed using markers for apoptosis and necrosis. Groups were compared using the students' t-test. RESULTS The number of lung metastases was significantly decreased in mice treated with RFA/IL2 (p=0.001) compared to IL2 (fig. 1A). RFA alone did not affect lung metastatic growth (fig. 1B). 77% (10/13) of RFA/IL2 treated mice did not have lung metastases (fig. 1C) compared to 0% in the other groups. RFA/IL2 treatment slightly increased NK cell levels. Antitumor activity of both CD8+ T cells and NK cells was subsequently confirmed in vitro. NK cells of RFA/IL2 or IL2 treated mice effectively killed tumor cells. Maximum cytotoxicity was observed with NK cells derived from RFA/IL2 treated mice. RFA/IL2 was the only treatment that yielded CD8+ T cells with specific antitumor cytotoxicity. RFA alone did not induce tumor specific cytotoxicity of both NK and CD8+ T cells. CONCLUSIONS This study shows that RFA combined with high-dose IL2 induces an antitumor immune response to mouse renal carcinoma cells that prevents the outgrowth of lung metastases. This effect may be mediated by both NK and CD8+ T cells. In conclusion, RFA could play a role in new multimodal treatment strategies to RCC. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e155 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Stephanie G.C. Kroeze Utrecht, Netherlands More articles by this author Maarten W. Nijkamp Utrecht, Netherlands More articles by this author Jeanine M.L. Roodhart Utrecht, Netherlands More articles by this author Gijsbert C. de Gast Amsterdam, Netherlands More articles by this author J.L.H. Ruud Bosch Utrecht, Netherlands More articles by this author Judith J.M. Jans Utrecht, Netherlands More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...