Exploitation of interleukin-18 by gastric cancers for their growth and evasion of host immunity

✍ Scribed by Takashi Majima; Takashi Ichikura; Kentaro Chochi; Toshinobu Kawabata; Hironori Tsujimoto; Hidekazu Sugasawa; Noritsugu Kuranaga; Eiji Takayama; Manabu Kinoshita; Hoshio Hiraide; Shuhji Seki; Hidetaka Mochizuki

• Book ID: 102274607
• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: French
• Weight: 312 KB
• Volume: 118
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.21334

✦ Synopsis

Interleukin-18 (IL-18) is a pleiotropic cytokine that enhances Th1 or Th2 immune response. We show a novel mechanism of gastric cancer cells that allows their immune escape utilizing IL-18. All 4 gastric cancer cell lines, but not colon lines, constitutively expressed IL-18 receptors and IL-18 dose-dependently enhanced their in vitro proliferation accompanied by nuclear factor kappaB activation. When IL-18-pretreated gastric cancer cells were cultured with cytokine-activated peripheral blood killer lymphocytes, the antitumor machineries, perforin or interferon-gamma production of killer lymphocytes decreased, resulting in a decreased susceptibility of cancer cells to killer lymphocytes. Furthermore, gastric cancer cells cultured with IL-18 showed an increased expression of a granzyme B inhibitor, protease inhibitor 9. IL-18 injections into severe combined immuno-deficient mice intraperitoneally inoculated with gastric cancer cells consistently decreased the mouse survival time. Our results indicate that gastric cancers exploit IL-18 to grow/invade and evade immunosurveillance in the hosts.