title: Attenuated Salmonella typhimurium prevents the establishment of unresectable hepatic metastases and improves survival in a murine model.
abstract: OBJECTIVE
  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.
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors.forename: Leland J
authors.initials: LJ
authors.lastname: Soto
authors.forename: Brent S
authors.initials: BS
authors.lastname: Sorenson
authors.forename: Adam S
authors.initials: AS
authors.lastname: Kim
authors.forename: Brad A
authors.initials: BA
authors.lastname: Feltis
authors.forename: Arnold S
authors.initials: AS
authors.lastname: Leonard
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Saltzman
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000517:prevention & control / Q000556:secondary; D000818:Animals; D018791:CD4 Lymphocyte Count; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000235:genetics*; D007694:Killer Cells, Natural; D008113:Liver Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary*; D016131:Lymphocyte Subsets; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D012486:Salmonella typhimurium / Q000235:genetics*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D007376:Interleukin-2