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Clinical and Developmental Immunology
Volume 2007, Article ID 17315, 9 pages
Research Article

Defective Differentiation of Myeloid and Plasmacytoid Dendritic Cells in Advanced Cancer Patients is not Normalized by Tyrosine Kinase Inhibition of the Vascular Endothelial Growth Factor Receptor

1Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, HV Amsterdam 1081, The Netherlands
2Department of Pathology, VU University Medical Center, De Boelelaan 1117, HV Amsterdam 1081, The Netherlands

Received 29 June 2007; Accepted 29 October 2007

Academic Editor: Mario Clerici

Copyright © 2007 H. van Cruijsen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Tumor-derived vascular endothelial growth factor (VEGF) has previously been identified as a causative factor in the disturbed differentiation of myeloid dendritic cells (DC) in advanced cancer patients. Here, we investigated the potential of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase (TK) inhibition to overcome this defective DC differentiation. To this end, peripheral blood DC (PBDC) precursor and subset frequencies were measured in 13 patients with advanced cancer before and after treatment with AZD2171, a TK inhibitor (TKI) of VEGFR, coadministered with gefitinib, and an epidermal growth factor receptor (EGFR) TKI. Of note, not only myeloid DC but also plasmacytoid DC frequencies were significantly reduced in the blood of the cancer patients prior to treatment, as compared to healthy controls. Moreover, besides an accumulated population of immature myeloid cells (ImC), a population of myeloid suppressor cells (MSC) was significantly increased. Upon systemic VEGFR TK inhibition, DC frequencies did not increase, whereas the rate of circulating MSC showed a slight, but not significant, decrease. In conclusion, TK inhibition of VEGFR with AZD2171 does not restore the defective PBDC differentiation observed in advanced cancer patients.