IFN-γ-dependent NK cell activation is essential to metastasis suppression by engineered Salmonella

Qiubin Lin, Li Rong, Xian Jia, Renhao Li, Bin Yu, Jingchu Hu, Xiao Luo, S. R. Badea, Chen Xu, Guofeng Fu, Kejiong Lai, Ming-chun Lee, Baozhong Zhang, Huarui Gong, Nan Zhou, Xiao Lei Chen, Shu-hai Lin (), Guo Fu () and Jian-Dong Huang ()
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Qiubin Lin: The University of Hong Kong
Li Rong: The University of Hong Kong
Xian Jia: Xiamen University
Renhao Li: The University of Hong Kong
Bin Yu: The University of Hong Kong
Jingchu Hu: Chinese Academy of Sciences
Xiao Luo: Chinese Academy of Sciences
S. R. Badea: The University of Hong Kong
Chen Xu: The University of Hong Kong
Guofeng Fu: Xiamen University
Kejiong Lai: Xiamen University
Ming-chun Lee: The University of Hong Kong
Baozhong Zhang: Chinese Academy of Sciences
Huarui Gong: The University of Hong Kong
Nan Zhou: Chinese Academy of Sciences
Xiao Lei Chen: Xiamen University
Shu-hai Lin: Xiamen University
Guo Fu: Xiamen University
Jian-Dong Huang: The University of Hong Kong

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Metastasis accounts for 90% of cancer-related deaths and, currently, there are no effective clinical therapies to block the metastatic cascade. A need to develop novel therapies specifically targeting fundamental metastasis processes remains urgent. Here, we demonstrate that Salmonella YB1, an engineered oxygen-sensitive strain, potently inhibits metastasis of a broad range of cancers. This process requires both IFN-γ and NK cells, as the absence of IFN-γ greatly reduces, whilst depletion of NK cells in vivo completely abolishes, the anti-metastatic ability of Salmonella. Mechanistically, we find that IFN-γ is mainly produced by NK cells during early Salmonella infection, and in turn, IFN-γ promotes the accumulation, activation, and cytotoxicity of NK cells, which kill the metastatic cancer cells thus achieving an anti-metastatic effect. Our findings highlight the significance of a self-regulatory feedback loop of NK cells in inhibiting metastasis, pointing a possible approach to develop anti-metastatic therapies by harnessing the power of NK cells.

Date: 2021
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DOI: 10.1038/s41467-021-22755-3

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