IFN-γ enhances the antitumor activity of attenuated salmonella-mediated cancer immunotherapy by increasing M1 macrophage and CD4 and CD8 T cell counts and decreasing neutrophil counts

Huimin Xu; Linghua Piao; Yundi Wu; Xiande Liu

doi:10.3389/fbioe.2022.996055

IFN-γ enhances the antitumor activity of attenuated salmonella-mediated cancer immunotherapy by increasing M1 macrophage and CD4 and CD8 T cell counts and decreasing neutrophil counts

Front Bioeng Biotechnol. 2022 Sep 29:10:996055. doi: 10.3389/fbioe.2022.996055. eCollection 2022.

Authors

Huimin Xu¹, Linghua Piao², Yundi Wu³, Xiande Liu¹

Affiliations

¹ School of Life Sciences, Hainan University, Haikou, China.
² Department of Physiology, Hainan Medical University, Haikou, China.
³ State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, Haikou, China.

Abstract

Bacteria-mediated cancer immunotherapy (BCI) inhibits tumor progression and has a synergistic antitumor effect when combined with chemotherapy. The anti- or pro-tumorigenic effects of interferon-γ (IFN-γ) are controversial; hence, we were interested in the antitumor effects of IFN-γ/BCI combination therapy. Here, we demonstrated that IFN-γ increased the tumor cell killing efficacy of attenuated Salmonella by prolonging the survival of tumor-colonizing bacteria via blockade of tumor-infiltrating neutrophil recruitment. In addition, IFN-γ attenuated Salmonella-stimulated immune responses by stimulating tumor infiltration by M1-like macrophages and CD4⁺ and CD8⁺ T cells, thereby facilitating tumor eradication. Taken together, these findings suggest that combination treatment with IFN-γ boosts the therapeutic response of BCI with S. tΔppGpp, suggesting that IFN-γ/BCI is a promising approach to immunotherapy.

Keywords: BCI; IFN-γ; S.tΔppGpp; T cell; macrophage; neutrophil.