Intratumoral injection of attenuated Salmonella vaccine can induce tumor microenvironmental shift from immune suppressive to immunogenic

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-Ghigh 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.

► Attenuated Salmonella vaccine (RASV) significantly inhibited tumor growth. ► RASV significantly increased TNF-α-secreting CD11b+Gr-1+ myeloid cells. ► RASV significantly reduced CD4+CD25+Foxp3+ Tregs. ► RASV can induce a tumor microenvironmental shift from suppressive to immunogenic.