Attenuated Salmonella typhimurium prevents the establishment of unresectable hepatic metastases and improves survival in a murine model.
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.
Soto
Leland J
LJ
Section of Pediatric Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Sorenson
Brent S
BS
Kim
Adam S
AS
Feltis
Brad A
BA
Leonard
Arnold S
AS
Saltzman
Daniel A
DA
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
D007376:Interleukin-2