Attenuated Salmonella typhimurium prevents the establishment of unresectable hepatic metastases and improves survival in a murine model

J Pediatr Surg. 2003 Jul;38(7):1075-9. doi: 10.1016/s0022-3468(03)00196-9.


Purpose: The authors investigated the utility of attenuated Salmonella typhimurium for preventing the establishment of hepatic metastases in a murine model.

Methods: A single, oral 10(8) cfu dose of attenuated S typhimurium was given 8 days before the establishment of a model of unresectable hepatic metastases. Animals were assessed for hepatic tumor number and volume, hepatic lymphocyte population analysis, and survival.

Results: Pretreatment with Salmonella provided a 10-fold reduction in hepatic tumor burden compared with saline-treated controls. The antitumor effect is associated with markedly elevated natural killer (NK), CD8+ and CD4+ hepatic lymphocytes. Pretreatment with Salmonella provided a 90-day survival rate of 30%, whereas control animals were dead by 30 days. All long-term survivors were devoid of hepatic tumor.

Conclusions: Attenuated S typhimurium effectively prevents the establishment of hepatic metastases in a murine model, providing a clear survival benefit. Thus, it may represent a novel form of in vivo immunotherapy for the prevention of hepatic metastases for patients with locally advanced colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / prevention & control
  • Adenocarcinoma / secondary
  • Animals
  • CD4 Lymphocyte Count
  • Female
  • Humans
  • Immunotherapy / methods*
  • Interleukin-2 / genetics*
  • Killer Cells, Natural
  • Liver Neoplasms / immunology
  • Liver Neoplasms / prevention & control*
  • Liver Neoplasms / secondary*
  • Lymphocyte Subsets
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Salmonella typhimurium / genetics*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • Interleukin-2