563 IL-17 PRODUCTION BY γδ T CELLS IS IMPORTANT FOR THE ANTITUMOR EFFECT OF MYCOBACTERIUM BOVIS BACILLUS CALMETTE-GUERIN TREATMENT AGAINST BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research I1 Apr 2012563 IL-17 PRODUCTION BY γδ T CELLS IS IMPORTANT FOR THE ANTITUMOR EFFECT OF MYCOBACTERIUM BOVIS BACILLUS CALMETTE-GUERIN TREATMENT AGAINST BLADDER CANCER Takashi Dejima, Ario Takeuchi, Masatoshi Eto, Tatsuya Nakatani, Yasunobu Yoshikai, and Seiji Naito Takashi DejimaTakashi Dejima Fukuoka, Japan More articles by this author , Ario TakeuchiArio Takeuchi Fukuoka, Japan More articles by this author , Masatoshi EtoMasatoshi Eto Kumamoto, Japan More articles by this author , Tatsuya NakataniTatsuya Nakatani Osaka, Japan More articles by this author , Yasunobu YoshikaiYasunobu Yoshikai Fukuoka, Japan More articles by this author , and Seiji NaitoSeiji Naito Fukuoka, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.638AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Intravesical inoculation of Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been used for the treatment of bladder cancer. However the antitumor effector mechanisms remain elusive. Recent studies demonstrated that neutrophils infiltrated in the bladder after BCG treatment played a key role in the antitumor effect. Interleukin (IL)-17 (also known as IL-17A) is a T cell-derived proinflammatory cytokine, which is involved in various pathogenesis where neutrophils are involved. However, at present, the mechanism of neutrophil infiltration after BCG treatment is not fully understood. METHODS γδ T cell-deficient (Cδ knock out (KO) and IL-17KO mice were kindly provided by Dr. S. Itohara and Dr. Y. Iwakura, respectively. The murine bladder cancer cell line, MB49, was kindly provided by Dr T. L. Ratliff. Mice were catheterized to receive an intravesical inoculate of 1 x 105 MB49 tumor cells on day 0. On days 1, 8, 15, and 22, mice were treated intravesically with either 3 x 106 CFU of BCG Connaught strain or PBS. Cytokines in the bladder were measured by ELISA. Cellular infiltrations in the bladder were analyzed by flow cytometry. For identification of IL-17-producing cells, intracellular cytokine staining method was used. RESULTS Significant infiltration of neutrophils was observed from one week after starting BCG treatment, and it gradually increased during the observation period. IL-17 production was induced as early as 1 day after BCG injection. During the course of repeated BCG administration, similar level of IL-17 production was induced after each injection. Infiltration of neutrophils was significantly reduced in IL-17KO mice. The control wild type (WT) mice treated with BCG exhibited significantly longer survival compared to PBS-treated mice. On the other hand, there was no difference in the survival between BCG- and PBS-treated IL-17KO mice. The major source of IL-17A was γδT cell population in the bladder. BCG-treated CδKO mice showed significant reduction of IL-17 production and neutrophil infiltration compared with BCG-treated control mice. On the other hand, there was no difference in either IL-17 production or neutrophil count between CD4 or NK cell-depleted mice and the control mice. Survival of CδKO mice was not improved by BCG treatment. CONCLUSIONS γδ T cells in the bladder have the anti tumor effect of intravesical BCG treatment via IL-17 production. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e230 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takashi Dejima Fukuoka, Japan More articles by this author Ario Takeuchi Fukuoka, Japan More articles by this author Masatoshi Eto Kumamoto, Japan More articles by this author Tatsuya Nakatani Osaka, Japan More articles by this author Yasunobu Yoshikai Fukuoka, Japan More articles by this author Seiji Naito Fukuoka, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...