Article abstract
Nature Biotechnology 25, 911 - 920 (2007)
Published online: 29 July 2007 | doi:10.1038/nbt1323
Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells
Farbod Shojaei1, Xiumin Wu1, Ajay K Malik1, Cuiling Zhong1, Megan E Baldwin1, Stefanie Schanz1, Germaine Fuh1, Hans-Peter Gerber1,2 & Napoleone Ferrara1
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.
- Genentech, Inc., 1 DNA Way, S. San Francisco, California 94080, USA.
- Present address: Seattle Genetics Inc., 21823 30th Drive, SE, Bothell, Washington 98021, USA.
Correspondence to: Farbod Shojaei1 e-mail: farbod@gene.com
Correspondence to: Napoleone Ferrara1 e-mail: nf@gene.com
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