IFN-? 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

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-gamma (IFN-gamma) are controversial; hence, we were interested in the antitumor effects of IFN-gamma/BCI combination therapy. Here, we demonstrated that IFN-gamma 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-gamma 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-gamma boosts the therapeutic response of BCI with S. t delta ppGpp, suggesting that IFN-gamma/BCI is a promising approach to immunotherapy.