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

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 engin...

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Veröffentlicht in:Nature communications 2021-05, Vol.12 (1), p.2537-2537, Article 2537
Hauptverfasser: Lin, Qiubin, Rong, Li, Jia, Xian, Li, Renhao, Yu, Bin, Hu, Jingchu, Luo, Xiao, Badea, S. R., Xu, Chen, Fu, Guofeng, Lai, Kejiong, Lee, Ming-chun, Zhang, Baozhong, Gong, Huarui, Zhou, Nan, Chen, Xiao Lei, Lin, Shu-hai, Fu, Guo, Huang, Jian-Dong
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Sprache:eng
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Zusammenfassung: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. Cancer metastasis is one of the major causes of cancer related deaths and there is an urgent need to find more clinically effective metastasis targeting agents. Here, the authors show that Salmonella YB1 inhibits metastasis in multiple mouse models of cancer through a mechanism dependent on IFN-γ and NK cells.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-22755-3