Abstracts
2000 Digestive Disease Week

# 2231 Attenuated Salmonella Reduces Hepatic Tumor Burden and Improves Survival in a Model of Murine Metastatic Colon Cancer.
Brad A. Feltis, Timothy Sielaff, David E. Sahar, Adam Kim, Daniel Saltzman, Carol Wells, Arnold Leonard, Minneapolis, MN

Nonspecific immune enhancement from infection may be associated with a reduction in metastatic cancer. An attenuated strain of Salmonella typhimurium (SAL) causes liver infection but remains clinically avirulent. We hypothesized that SAL would induce a localized hepatic immune response and improve survival in a murine model of metastatic colon cancer. Methods: Mice were orally inoculated with saline or 109 SAL; 24 hrs later, mice underwent laparotomy and 5x104 MCA38 murine adenocarcinoma cells were injected into the spleen. Four groups (8 mice/group) were studied: Control, SAL only, tumor only (T), and SAL+tumor (SAL+T). On day 14, liver tumors were counted and peripheral blood and hepatic lymphocytes were analyzed by FACScan (n=3/group). Survival was studied separately (10 mice/group). Results: SAL+T had fewer liver tumors compared to T (21±.6 vs 182±39, p<0.01, t-test). SAL+T also had improved survival compared to T (21±.6 d vs 18±.4 d, p<0.05, Wilcoxon ranked sum). All groups had increased NK+ lymphocytes in blood and liver compared to control (Table). Conclusion: Oral inoculation with S. typhimurium increased both hepatic and systemic NK+ lymphocytes, reduced hepatic tumor burden, and improved survival in this model. These results indicate that nonspecific immune enhancement resulting from infection may be therapeutic in the prevention of colorectal tumor metastasis.