Yusuke Matsumoto1, Hironori Tsujimoto2, Satoshi Ono3, Nariyoshi Shinomiya4, Hiromi Miyazaki3, Shuichi Hiraki1, Risa Takahata1, Kazumichi Yoshida1, Daizoh Saitoh3, Takao Yamori5, Junji Yamamoto1, Kazuo Hase1. 1. Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan. 2. Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan. tsujihi@ndmc.ac.jp. 3. Division of Traumatology, National Defense Medical College, Tokorozawa, Saitama, Japan. 4. Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan. 5. Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
Abstract
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.
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 murineliver 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:CLPmice 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 CLPmice on day 7 significantly decreased. The cytotoxic activities of liver MNCs were significantly suppressed in CLPmice 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 murineliver metastasis model, which may be partially caused by a decrease in the number and activity of NK cells during abdominal infection.
Authors: Peter Tschann; Markus P Weigl; Philipp Szeverinski; Daniel Lechner; Thomas Brock; Stephanie Rauch; Jana Rossner; Helmut Eiter; Paolo N C Girotti; Tarkan Jäger; Jaroslav Presl; Klaus Emmanuel; Alexander De Vries; Ingmar Königsrainer; Patrick Clemens Journal: Langenbecks Arch Surg Date: 2022-07-18 Impact factor: 2.895
Authors: Diego Vicente; Miguel Patino; Rebecca Marcus; Heather Lillmoe; Preparim Limani; Timothy Newhook; Andy Lee; Ching-Wei Tzeng; Yun Segraves-Chun; David Tweardy; Vijaya Gottumukkala; Jean-Nicolas Vauthey; Thomas Aloia; Juan P Cata Journal: Oncotarget Date: 2019-01-15