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Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
IFN-γ-dependent NK cell activation is essential to metastasis suppression by engineered Salmonella
Qiubin Lin1,2, Li Rong1, Xian Jia3
1School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
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.
Insights
Engineered Salmonella YB1 inhibits cancer metastasis by activating a feedback loop involving interferon-gamma (IFN-γ) and natural killer (NK) cells, offering a novel therapeutic strategy.
Area of Science:
- Oncology
- Immunology
- Microbiology
Background:
- Metastasis is responsible for 90% of cancer deaths, with limited effective therapies.
- Novel treatments targeting the metastatic cascade are urgently needed.
Purpose of the Study:
- To investigate the anti-metastatic potential of engineered Salmonella YB1.
- To elucidate the immunological mechanisms underlying Salmonella YB1's anti-metastatic effects.
Main Methods:
- Utilized an engineered oxygen-sensitive Salmonella strain (YB1).
- Assessed anti-metastatic efficacy across various cancer types.
- Investigated the roles of interferon-gamma (IFN-γ) and natural killer (NK) cells in vivo and in vitro.
Main Results:
- Salmonella YB1 demonstrated potent inhibition of metastasis in a broad range of cancers.
- The anti-metastatic effect was dependent on both IFN-γ and NK cells.
- IFN-γ, primarily produced by NK cells during early infection, enhances NK cell accumulation, activation, and cytotoxicity against metastatic cancer cells.
Conclusions:
- Salmonella YB1 effectively inhibits cancer metastasis through an NK cell-mediated mechanism.
- A self-regulatory feedback loop between NK cells and IFN-γ is crucial for anti-metastatic activity.
- Harnessing NK cell function presents a promising strategy for developing novel anti-metastatic therapies.
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