We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Tumor refractoriness to anti-VEGF treatment is mediated by CD11b<sup>+</sup>Gr1<sup>+</sup> myeloid cells.
- Authors
Shojaei, Farbod; Wu, Xiumin; Malik, Ajay K; Zhong, Cuiling; Baldwin, Megan E; Schanz, Stefanie; Fuh, Germaine; Gerber, Hans-Peter; Ferrara, Napoleone
- Abstract
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.
- Subjects
MONOCLONAL antibodies; GENETIC regulation; GROWTH factors; TUMORS; BONE marrow; CELL tumors
- Publication
Nature Biotechnology, 2007, Vol 25, Issue 8, p911
- ISSN
1087-0156
- Publication type
Article
- DOI
10.1038/nbt1323