A novel Salmonella Typhi-based immunotherapy promotes tumor killing via an antitumor Th1-type cellular immune response and neutrophil activation in a mouse model of breast cancer.

VENDRELL A; GRAVISACO M; PASETTI MF; CROCI M; COLOMBO L; RODRIGUEZ C; MONGINI C; WALNER C

VACCINE

ELSEVIER SCI LTD

Año: 2010 vol. 29 p. 728 - 736

0264-410X

We investigated the use of a live, attenuated Salmonella enterica serovar Typhivaccine strain as an antitumor immunotherapy. Mice bearing a subcutaneous tumor(LM3 mammary adenocarcinoma) were immunized on three occasions with S. Typhistrain CVD 915 by injection into the tumor, the peritumoral tissue and thedraining lymph node areas; this procedure was termed Salmonella multipletreatment (Salmonella MT). Tumor-bearing mice subjected to the Salmonella MTexhibited reduced tumor growth, prolonged survival and reduced incidence of lung metastases, compared to untreated mice. We examined the mechanisms mediating thiseffect and found that Salmonella MT promoted an antitumor Th1-type responsecharacterized by increased frequencies of IFN-ã-secreting CD4(+) T and CD8(+) Tcells with reduction of regulatory T cells in tumor draining lymph nodes. Themain cells infiltrating bacteria-treated tumors were activated neutrophils, whichcan exert an antitumor effect through the secretion of TNF-á. These resultsdemonstrate for the first time the efficacy of an attenuated S. Typhi vaccinestrain as a cancer immunotherapeutic agent. By potentiating the host antitumorimmune response, this approach could be a powerful adjunct tool for cancertherapy.