title: Intratumoral injection of attenuated Salmonella vaccine can induce tumor microenvironmental shift from immune suppressive to immunogenic.
abstract: Attenuated Salmonella vaccines show therapeutic anti-cancer effects, but the underlying mechanism has not been well investigated. In the current study, intratumoral (i.t.) injection of recombinant attenuated Salmonella enterica serovar Typhimurium vaccine (RASV) significantly inhibited Her-2/neu-expressing tumor growth. Although depletion of CD8(+) cells in RASV-treated mice significantly restored tumor growth, the induction of Her-2/neu-specific cytotoxic T lymphocytes (CTLs) was not well correlated with the generation of the anti-tumor effect. Therefore, we hypothesized that RASV might induce a tumor microenvironmental shift, from immune suppressive to immunogenic, to reduce the suppressive force and finally elicit a successful anti-tumor response. We found that i.t. injection of RASV significantly increased the level of CD11b(+)Gr-1(+) myeloid cells identified as myeloid-derived suppressor cell (MDSC), but a significant portion of these cells were TNF-α-secreting Ly6-G(high) subsets, which can function as antitumor effector cells. We further investigated whether RASV can modulate immunosuppressive Treg cells, and CD4(+)CD25(+) Foxp3(+) Tregs was significantly reduced in RASV-treated mice. Thus, i.t. injection of RASV may offer a novel anti-cancer approach by eliciting transformation of immunosuppressive MDSCs into TNF-α-secreting neutrophils and reducing the generation of Treg cells, especially in the presence of tumor-specific CTLs. Collectively, these data will provide us an insight for the development of new anti-tumor approaches to overcome the immunosuppressive environment generated by tumors.
authors: Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, 200-701, South Korea.
authors: Eun-Hye
authors: EH
authors: Hong
authors: Sun-Young
authors: SY
authors: Chang
authors: Bo-Ra
authors: BR
authors: Lee
authors: A-Rim
authors: AR
authors: Pyun
authors: Ji-Won
authors: JW
authors: Kim
authors: Mi-Na
authors: MN
authors: Kweon
authors: Hyun-Jeong
authors: HJ
authors: Ko
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007267:Injections / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D022562:Salmonella Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D007155:Immunologic Factors; D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic