CONICET | Buscador de Institutos y Recursos Humanos

We have previously demonstrated the anticancer properties of an attenuated Salmonella Typhi (S. Typhi) vaccine strain against a murine T-cell lymphoma (EL4). When mice bearing a subcutaneous tumor were immunized twice with Salmonella, by injection into the tumor and in the draining lymph node areas, a significant reduction in tumor size of bacteria-treated mice, as early as 5 days after the first treatment, and a prolonged survival compared to untreated mice, were observed. The aim of present study was to elucidate molecular and immune mechanisms related to the antitumor therapeutic effect mediated by Salmonella. Our results demonstrated that immunizations with bacteria induced T and B lymphocyte expansion in tumor draining lymph nodes, 7 days after the first treatment (p<0.05). To investigate the potential of T cell to collaborate in the antitumor therapeutic effect, we performed experiments applying the same immunotherapeutic schedule in EL4 tumor-bearing Nude mice, and evaluated survival time and tumor growth. No differences in survival time were found between control mice and Salmonella-treated animals (p>0.05). In contrast, tumor growth was significantly retarded in mice inoculated with these bacteria (p<0.05). These findings suggest that T cells could be involved in the increase of survival, whereas the reduction in tumor size seems to be T-cell independent. Our study also demonstrates that EL4 cells fail to proliferate and die (p<0.01), in a time and dose-dependent fashion, when cocultured with Salmonella. Acridine orange-ethidium bromide staining of tumor cells suggests that bacteria-induced tumor cell death is mediated by apoptosis. These immune mechanisms could have in vivo relevance and thus contribute to eliciting antitumor immunity in mice treated with Salmonella. Overall, our study illustrates the potential usefulness of S. Typhi in immunotherapy against malignant tumors