title: Attenuated mutant strain of Salmonella Typhimurium lacking the ZnuABC transporter contrasts tumor growth promoting anti-cancer immune response.
abstract: Salmonella Typhimurium has been shown to be highly effective as antitumor agent. The aim of this study was to investigate the tumor targeting efficacy and the mechanism of action of a specific attenuated mutant strain of Salmonella Typhimurium (STM) devoid of the whole operon coding for the high-affinity zinc transporter ZnuABC, which is required for bacterial growth in environments poor in zinc and for conferring full virulence to different Gram-negative pathogens.We showed that STM is able to penetrate and replicate into tumor cells in in vitro and in vivo models. The subcutaneous administration of STM in mammary adenocarcinoma mouse model led to both reduction of tumor growth and increase in life expectancy of STM treated mice. Moreover, investigating the potential mechanism behind the favorable clinical outcomes, we provide evidence that STM stimulates a potent inflammatory response and a specific immune pattern, recruiting a large number of innate and adaptive immune cells capable to contrast the immunosuppressive environment generated by tumors.
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome 00161, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Chirullo
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome 00133, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Ammendola
authors.affiliation: Università degli Studi di Perugia, Department of Veterinary Medicine, Perugia 06126, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Leonardi
authors.affiliation: Veterinary Clinic, Rieti 02043, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Falcini
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome 00161, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Petrucci
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome 00161, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pistoia
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome 00161, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vendetti
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome 00133, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Battistoni
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome 00161, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pasquali
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000172:deficiency; D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007167:Immunotherapy / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012486:Salmonella typhimurium / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents
keywords: antitumor efficacy; attenuated-Salmonella; bacterial therapy; cancer therapy; immune response