Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells

Nat Biotechnol. 2007 Aug;25(8):911-20. doi: 10.1038/nbt1323. Epub 2007 Jul 29.


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.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • CD11b Antigen / metabolism*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / metabolism*
  • Receptors, Chemokine / metabolism*
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*


  • Antineoplastic Agents
  • CD11b Antigen
  • Gr-1 protein, mouse
  • Receptors, Chemokine
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse