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Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells.
Nature Immunology ( IF 30.5 ) Pub Date : 2017-Sep-01 , DOI: 10.1038/ni.3800
Yulong Gao , Fernando Souza-Fonseca-Guimaraes , Tobias Bald , Susanna S Ng , Arabella Young , Shin Foong Ngiow , Jai Rautela , Jasmin Straube , Nic Waddell , Stephen J Blake , Juming Yan , Laurent Bartholin , Jason S Lee , Eric Vivier , Kazuyoshi Takeda , Meriem Messaoudene , Laurence Zitvogel , Michele W L Teng , Gabrielle T Belz , Christian R Engwerda , Nicholas D Huntington , Kyohei Nakamura , Michael Hölzel , Mark J Smyth

Avoiding destruction by immune cells is a hallmark of cancer, yet how tumors ultimately evade control by natural killer (NK) cells remains incompletely defined. Using global transcriptomic and flow-cytometry analyses and genetically engineered mouse models, we identified the cytokine-TGF-β-signaling-dependent conversion of NK cells (CD49a-CD49b+Eomes+) into intermediate type 1 innate lymphoid cell (intILC1) (CD49a+CD49b+Eomes+) populations and ILC1 (CD49a+CD49b-Eomesint) populations in the tumor microenvironment. Strikingly, intILC1s and ILC1s were unable to control local tumor growth and metastasis, whereas NK cells favored tumor immunosurveillance. Experiments with an antibody that neutralizes the cytokine TNF suggested that escape from the innate immune system was partially mediated by TNF-producing ILC1s. Our findings provide new insight into the plasticity of group 1 ILCs in the tumor microenvironment and suggest that the TGF-β-driven conversion of NK cells into ILC1s is a previously unknown mechanism by which tumors escape surveillance by the innate immune system.

中文翻译:

通过将效应子NK细胞转化为1型先天淋巴样细胞来进行肿瘤免疫逃避。

避免被免疫细胞破坏是癌症的标志,但肿瘤最终如何逃避自然杀伤(NK)细胞的控制仍未完全确定。使用整体转录组学和流式细胞仪分析以及基因工程小鼠模型,我们确定了NK细胞(CD49a - CD49b + Eomes +)向中间1型先天性淋巴样细胞(intILC1)(CD49a)的细胞因子-TGF-β-信号依赖性转化+ CD49b + Eomes +)人口和ILC1(CD49a + CD49b - Eomes int)肿瘤微环境中的种群。令人惊讶的是,intILC1和ILC1无法控制局部肿瘤的生长和转移,而NK细胞则有利于肿瘤的免疫监视。用中和细胞因子TNF的抗体进行的实验表明,先天免疫系统的逃逸部分由产生TNF的ILC1介导。我们的发现为肿瘤微环境中第1组ILC的可塑性提供了新的见识,并表明TGF-β驱动的NK细胞向ILC1s的转化是肿瘤逃避先天免疫系统监视的先前未知的机制。
更新日期:2017-09-06
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