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

Leland J. Soto, Brent S. Sorenson, Adam S. Kim, Brad A. Feltis, Arnold S. Leonard, Daniel A Saltzman

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17 Scopus citations

Abstract

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 108 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.

Original languageEnglish (US)
Pages (from-to)1075-1079
Number of pages5
JournalJournal of Pediatric Surgery
Volume38
Issue number7
DOIs
StatePublished - Jul 1 2003

Keywords

  • Cancer
  • Metastases
  • Prevention
  • Salmonella

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