Gr-1+CD11b+ myeloid cells tip the balance of immune protection to tumor promotion in the premetastatic lung.
Gr-1+CD11b+ myeloid cells tip the balance of immune protection to tumor promotion in the premetastatic lung.
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GR-1+ CD11b+髓样细胞将免疫保护对肿瘤促进的平衡促进了前转移性肺的促进。
DOI：
10.1158/0008-5472.can-10-0706
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发表时间：
2010-08-01
期刊：
影响因子：
11.2
通讯作者：
Yang L
中科院分区：
文献类型：
--
作者：
Yan HH;Pickup M;Pang Y;Gorska AE;Li Z;Chytil A;Geng Y;Gray JW;Moses HL;Yang L
原发肿瘤在肿瘤细胞到达之前影响选定的远处器官的机制仍有待阐明。结果表明，荷瘤小鼠肺中Gr-1+CD11b+细胞在肿瘤细胞到来前显著增加。在转移前的肺中，这些未成熟的髓系细胞显著减少干扰素-γ的产生，并增加促炎细胞因子。此外，它们还能产生大量的基质金属蛋白酶9(MMP9)，促进血管重塑。MMP9的缺失可使转移前肺的异常血管结构正常化，减少肺转移。MMP9的产生和活性选择性地局限于肺和具有大量Gr-1+CD11b+细胞的器官。我们的工作揭示了Gr-1+CD11b+细胞的一种新的促肿瘤机制，该机制将转移前的肺改变为炎症和增殖环境，削弱免疫保护，并通过异常的血管形成促进转移。因此，抑制Gr-1+CD11b+细胞可以改善转移前肺环境，改善宿主免疫监视，抑制肿瘤转移。
The mechanisms by which a primary tumor affects a selected distant organ before tumor cell arrival remain to be elucidated. This report shows that Gr-1+CD11b+ cells are significantly increased in lungs of mice bearing mammary adenocarcinomas before tumor cell arrival. In the premetastatic lungs, these immature myeloid cells significantly decrease IFN-γ production and increase proinflammatory cytokines. In addition, they produce large quantities of matrix metalloproteinase 9 (MMP9) and promote vascular remodeling. Deletion of MMP9 normalizes aberrant vasculature in the premetastatic lung and diminishes lung metastasis. The production and activity of MMP9 is selectively restricted to lungs and organs with a large number of Gr-1+CD11b+ cells. Our work reveals a novel protumor mechanism for Gr-1+CD11b+ cells that changes the premetastatic lung into an inflammatory and proliferative environment, diminishes immune protection, and promotes metastasis through aberrant vasculature formation. Thus, inhibition of Gr-1+CD11b+ cells could normalize the premetastatic lung environment, improve host immunosurveillance, and inhibit tumor metastasis.