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

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Acknowledgment

The authors are grateful to Kouji Matsumura (Central Research Laboratory, National Defense Medical College, Saitama, Japan) for his technical support concerning cell culture.

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan

    Yusuke Matsumoto MD, PhD, Hironori Tsujimoto MD, PhD, Shuichi Hiraki MD, PhD, Risa Takahata MD, PhD, Kazumichi Yoshida MD, PhD, Junji Yamamoto MD, PhD & Kazuo Hase MD, PhD

  2. Division of Traumatology, National Defense Medical College, Tokorozawa, Saitama, Japan

    Satoshi Ono MD, PhD, Hiromi Miyazaki PhD & Daizoh Saitoh MD, PhD

  3. Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan

    Nariyoshi Shinomiya MD, PhD

  4. Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan

    Takao Yamori PhD

Authors
  1. Yusuke Matsumoto MD, PhD
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  2. Hironori Tsujimoto MD, PhD
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  3. Satoshi Ono MD, PhD
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  6. Shuichi Hiraki MD, PhD
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  12. Kazuo Hase MD, PhD
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Corresponding author

Correspondence to Hironori Tsujimoto MD, PhD.

Electronic supplementary material

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10434_2015_4466_MOESM1_ESM.pdf

Analyses of cytokine levels in the liver homogenates in CLP and sham mice without tumor inoculation. There were no differences of cytokine levels in the liver homogenates in CLP and sham mice without tumor inoculation (n=4). Each experiment was independently performed 3 times with similar results. Representative data are depicted.White bar = sham mice, black bars = CLP mice (PDF 29 kb)

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Matsumoto, Y., Tsujimoto, H., Ono, S. et al. Abdominal Infection Suppresses the Number and Activity of Intrahepatic Natural Killer Cells and Promotes Tumor Growth in a Murine Liver Metastasis Model. Ann Surg Oncol 23 (Suppl 2), 257–265 (2016). https://doi.org/10.1245/s10434-015-4466-7

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  • DOI: https://doi.org/10.1245/s10434-015-4466-7

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