IFN-γ-dependent NK cell activation is essential to metastasis suppression by engineered Salmonella.
IFN-γ-dependent NK cell activation is essential to metastasis suppression by engineered Salmonella.
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IFN-γ依赖性 NK 细胞激活对于工程沙门氏菌的转移抑制至关重要
DOI：
10.1038/s41467-021-22755-3
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发表时间：
2021-05-05
影响因子：
16.6
通讯作者：
Huang JD
中科院分区：
文献类型：
--
作者：
Lin Q;Rong L;Jia X;Li R;Yu B;Hu J;Luo X;Badea SR;Xu C;Fu G;Lai K;Lee MC;Zhang B;Gong H;Zhou N;Chen XL;Lin SH;Fu G;Huang JD
转移占癌症相关死亡的90%，目前还没有有效的临床疗法来阻止转移级联反应。开发专门针对基础转移过程的新疗法的需求仍然迫切。在这里，我们证明了沙门氏菌YB1，一种工程氧敏感菌株，有效地抑制了广泛范围的癌症的转移。这一过程需要干扰素-γ和NK细胞，因为干扰素-γ的缺失大大降低了沙门氏菌的抗转移能力，而体内NK细胞的耗尽则完全消除了这一过程。从机制上讲，我们发现在沙门氏菌感染早期，干扰素-γ主要由NK细胞产生，进而促进NK细胞的聚集、活化和细胞毒作用，从而杀灭转移的癌细胞，从而达到抗转移的作用。我们的发现强调了NK细胞的自我调节反馈环在抑制转移方面的重要性，为利用NK细胞的力量开发抗转移治疗指明了一条可能的途径。肿瘤转移是导致肿瘤相关死亡的主要原因之一，迫切需要寻找更有效的临床转移靶向药物。在这里，作者表明，沙门氏菌YB1通过依赖干扰素-γ和NK细胞的机制抑制多种小鼠癌症模型的转移。
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.
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影响因子：
30.5
作者：
通讯作者：
--
影响因子：
64.8
作者：
Finisguerra V;Di Conza G;Di Matteo M;Serneels J;Costa S;Thompson AA;Wauters E;Walmsley S;Prenen H;Granot Z;Casazza A;Mazzone M
通讯作者：
Mazzone M
影响因子：
15.9
作者：
Eyles, Jo;Puaux, Anne-Laure;Abastado, Jean-Pierre
通讯作者：
Abastado, Jean-Pierre
DOI：
10.1038/nrc3004
发表时间：
2011-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Gay LJ;Felding-Habermann B
通讯作者：
Felding-Habermann B
影响因子：
64.5
作者：
Gao, Jianjun;Shi, Lewis Zhichang;Zhao, Hao;Chen, Jianfeng;Xiong, Liangwen;He, Qiuming;Chen, Tenghui;Roszik, Jason;Bernatchez, Chantale;Woodman, Scott E.;Chen, Pei-Ling;Hwu, Patrick;Allison, James P.;Futreal, Andrew;Wargo, Jennifer A.;Sharma, Padmanee
通讯作者：
Sharma, Padmanee