A SALMONELLA-BASED CANCER IMMUNOTHERAPY PROMOTES ANTITUMOR EFFECT AND REDUCTION OF SPONTANEOUS LUNG METASTASES

VENDRELL A; GRAVISACO M; CROCI M; RODRIGUEZ C; MONGINI C.; WALDNER C

Viña del Mar. Chile

Congreso; 9th Latin American Congress of Immunology; 2009

9th Latin American Congress of Immunology

Previously we demonstrated that a novel Salmonella immunotherapy reduced tumor growth and prolonged survival in a murine mammary adenocarcinoma (LM3). We found that Salmonella treatment promoted a Th1-type response characterized by increased frequencies of IFN-gamma-secreting CD4+ T cells with reduction of regulatory T cells in draining lymph nodes. In this study we further characterized the antitumor effect of this cancer immunotherapy. Mice bearing a LM3 tumor were immunized with attenuated Salmonella Typhi by injection into the tumor, in peritumoral tissue and in the draining lymph node areas. Then, the invasiveness and incidence of metastases were investigated. Salmonella injected tumors showed less invasion of surrounding adipose, muscular and mammary tissue compared with control ones. Moreover, a marked decrease in the incidence of lung metastases was observed in mice subjected to Salmonella treatment compared with untreated mice (p<0.05). Furthermore, after intratumoral bacteria inoculation, tumors were highly infiltrated by neutrophils which were able to secrete TNF-alpha and IFN-gamma; these results suggest a potential role of neutrophils in Salmonella-based antitumor response. In conclusion, Salmonella treatment inhibited the invasive and metastatic properties of LM3 cells. This immunotherapeutic approach could be used in the treatment of different forms of cancer, including those that generate metastasis