2000 Abstract: 2231: Attenuated Salmonella Reduces Hepatic Tumor Burden and Improves Survival in a Model of Murine Metastatic Colon Cancer.
Abstracts
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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. |
