title: 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.
abstract: We investigated the use of a live, attenuated Salmonella enterica serovar Typhi vaccine strain as an antitumor immunotherapy. Mice bearing a subcutaneous tumor (LM3 mammary adenocarcinoma) were immunized on three occasions with S. Typhi strain CVD 915 by injection into the tumor, the peritumoral tissue and the draining lymph node areas; this procedure was termed Salmonella multiple treatment (Salmonella MT). Tumor-bearing mice subjected to the Salmonella MT exhibited reduced tumor growth, prolonged survival and reduced incidence of lung metastases, compared to untreated mice. We examined the mechanisms mediating this effect and found that Salmonella MT promoted an antitumor Th1-type response characterized by increased frequencies of IFN-γ-secreting CD4(+) T and CD8(+) T cells with reduction of regulatory T cells in tumor draining lymph nodes. The main cells infiltrating bacteria-treated tumors were activated neutrophils, which can exert an antitumor effect through the secretion of TNF-α. These results demonstrate for the first time the efficacy of an attenuated S. Typhi vaccine strain as a cancer immunotherapeutic agent. By potentiating the host antitumor immune response, this approach could be a powerful adjunct tool for cancer therapy.
authors.affiliation: Centro de Estudios Farmacológicos y Botánicos-Consejo Nacional de Investigaciones Científicas y Técnicas (CEFyBO-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Alejandrina
authors.initials: A
authors.lastname: Vendrell
authors.forename: María J
authors.initials: MJ
authors.lastname: Gravisaco
authors.forename: Marcela F
authors.initials: MF
authors.lastname: Pasetti
authors.forename: Máximo
authors.initials: M
authors.lastname: Croci
authors.forename: Lucas
authors.initials: L
authors.lastname: Colombo
authors.forename: Carla
authors.initials: C
authors.lastname: Rodríguez
authors.forename: Claudia
authors.initials: C
authors.lastname: Mongini
authors.forename: Claudia I
authors.initials: CI
authors.lastname: Waldner
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007111:Immunity, Cellular; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000517:prevention & control; D018375:Neutrophil Activation; D012485:Salmonella typhi / Q000276:immunology*; D016019:Survival Analysis; D018417:Th1 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014611:Vaccination / Q000379:methods; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D014409:Tumor Necrosis Factor-alpha; D014613:Vaccines, Attenuated