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有缺陷的分化的骨髓血浆树突细胞在晚期癌症患者并不是标准化的酪氨酸激酶抑制血管内皮生长因子受体.pdfVIP

Hindawi Publishing Corporation Clinical and Developmental Immunology Volume 2007, Article ID 17315, 9 pages doi:10.1155/2007/17315 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 H. van Cruijsen,1 K. Hoekman,1 A. G. M. Stam,2 A. J. M. van den Eertwegh,1 B. C. Kuenen,1 R. J. Scheper,2 G. Giaccone,1 and T. D. de Gruijl1 1 Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands 2 Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands Correspondence should be addressed to H. van Cruijsen, h.vancruijsen@vumc.nl Received 29 June 2007; Accepted 29 October 2007 Recommended by Mario Clerici 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 en- dothelial 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 fac- tor 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 (