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

IFN-γ 通过增加 M1 巨噬细胞和 CD4 和 CD8 T 细胞计数并减少中性粒细胞计数来增强减毒沙门氏菌介导的癌症免疫疗法的抗肿瘤活性

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作者:Huimin Xu, Linghua Piao, Yundi Wu, Xiande Liu

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.

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