Abdominal Infection Suppresses the Number and Activity of Intrahepatic Natural Killer Cells and Promotes Tumor Growth in a Murine Liver Metastasis Model

• Published in: Annals of surgical oncology 2016-02, Vol.23 (Suppl 2), p.257-265
• Main Authors: Matsumoto, Yusuke, Tsujimoto, Hironori, Ono, Satoshi, Shinomiya, Nariyoshi, Miyazaki, Hiromi, Hiraki, Shuichi, Takahata, Risa, Yoshida, Kazumichi, Saitoh, Daizoh, Yamori, Takao, Yamamoto, Junji, Hase, Kazuo
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Colonic Neoplasms - immunology; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Cytokines - metabolism; Disease Models, Animal; Female; Flow Cytometry; Gastrointestinal Oncology; Humans; Immunoenzyme Techniques; Intraabdominal Infections - physiopathology; Killer Cells, Natural - immunology; Killer Cells, Natural - pathology; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - pathology; Liver Neoplasms - immunology; Liver Neoplasms - metabolism; Liver Neoplasms - secondary; Medicine; Medicine & Public Health; Mice; Mice, Inbred BALB C; Oncology; Peritonitis - etiology; Peritonitis - pathology; Surgery; Surgical Oncology; Survival Rate; Tumor Cells, Cultured
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-015-4466-7

Background Increasing evidence suggests that postoperative infection is associated with poorer long-term outcome in various malignancies. However, the mechanism of poor prognosis induced by postoperative infection has not been clearly explained. We sought to determine whether abdominal infection promotes cancer metastases in a murine liver metastasis model, and to investigate the role of liver natural killer (NK) cells on antitumor immunity during abdominal infection. Methods Female BALB/c (8–10 weeks old) mice were inoculated with NL-17 colon cancer cells into the spleen and then subjected to abdominal infection induced by cecal ligation and puncture (CLP) or sham treatment. The extent of liver metastases and cytokine production in the serum and liver were investigated. Cell fraction and cytotoxic activities of liver mononuclear cells (MNCs) were elucidated. Results CLP mice had poorer survival and their serum levels of IL-6, -10, and -12p70 were significantly elevated on day 1 compared with sham-treated and control mice. No obvious differences in cytokine levels of the liver homogenates were identified among the three groups, except IL-12p70 levels in CLP mice on day 7 significantly decreased. The cytotoxic activities of liver MNCs were significantly suppressed in CLP mice soon after tumor inoculation. Flow cytometry revealed a decrease in NK cells in the liver and perforin and granzyme B expression levels. Conclusions Abdominal infection promoted liver metastases in a murine liver metastasis model, which may be partially caused by a decrease in the number and activity of NK cells during abdominal infection.