Cancer Immunotherapy based on Salmonella administration induces antitumor effect. Role of neutrophils, effector and regulatory T cells in Salmonella induced tumor immunity

VENDRELL ALEJANDRINA; GRAVISACO MARÍA JOSÉ; CROCI MáXIMO; MONGINI C; WADNER CI

Tandil, Buenos Aires

Congreso; XL Reunion Anual de la Sociedad Argentina de Farmacologia Experimental; 2008

Sociedad Argentina de Farmacologia Experimental

We have previously demonstrated that a novel Salmonella immunotherapy induced a significant reduction in tumor size and prolonged survival in mice bearing the mammary adenocarcinoma LM3. The aim of this study is to elucidate the immune mechanisms regulated by Salmonella to achieve this antitumor response. BALB/c mice were subcutaneously inoculated with LM3 tumor cells. When tumors were palpable, groups of animals were immunized twice with bacteria or PBS, either intratumoral or in the peritumoral and in the tumor-draining lymph nodes (TDLNs) area. After 14 days of the first immunization, mice were sacrified to study antitumor response in TDLNs and tumors. Our results indicate that Salmonella promotes activation of CD4+ and CD8+ effector T cells producing IFN-gamma, and reduction of T regulatory cells in TDLNs respect to PBS-treated mice (p < 0.05). Moreover, we found that neutrophils are the most important cells infiltrating bacteria-infected tumors, exerting antitumor effect probably by IFN-gamma and TNF-alfa secretion. In conclusion, we demonstrated that the anticancer therapeutic properties of Salmonella are mediated by induction of both innate and adaptive immune mechanisms to overcome immune tolerance to tumors.