Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells
Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells
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DOI：
10.1038/nbt1323
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发表时间：
2007-08-01
影响因子：
46.9
通讯作者：
Ferrara, Napoleone
中科院分区：
文献类型：
--
作者：
Shojaei, Farbod;Wu, Xiumin;Ferrara, Napoleone
Vascular endothelial growth factor ( VEGF) is an essential regulator of normal and abnormal blood vessel growth. A monoclonal antibody ( mAb) that targets VEGF suppresses tumor growth in murine cancer models and human patients. We investigated cellular and molecular events that mediate refractoriness of tumors to anti-angiogenic therapy. Inherent anti-VEGF refractoriness is associated with infiltration of the tumor tissue by CD11b(+)Gr1(+) myeloid cells. Recruitment of these myeloid cells is also sufficient to confer refractoriness. Combining anti-VEGF treatment with a mAb that targets myeloid cells inhibits growth of refractory tumors more effectively than anti-VEGF alone. Gene expression analysis in CD11b(+)Gr1(+) cells isolated from the bone marrow of mice bearing refractory tumors reveals higher expression of a distinct set of genes known to be implicated in active mobilization and recruitment of myeloid cells. These findings indicate that, in our models, refractoriness to anti-VEGF treatment is determined by the ability of tumors to prime and recruit CD11b(+)Gr1(+) cells.
