Dendritic cell (DC) enhances VEGF clearance from neuroblastoma - a mechanism for DC-based immunotherapy

Abstract

Aim of the Study: Vascular endothelial growth factor (VEGF) is up-regulated in a number of tumor types including neuroblastoma. It has been reported that VEGF expression is inversely correlated with dendritic cells (DCs) infiltration in tumor specimens. Furthermore, the plasma levels of VEGF in tumor patients decreased during DC-based immunotherapy. Therefore, our hypothesis is whether DCs have a capacity to clear VEGF. Methods: Monocyte-derived DCs were co-cultured with supernatants from neuroblastoma cell culture containing large amount of VEGF (tumor conditioned medium, TCM) and recombinant human VEGF (rh VEGF), respectively. The concentrations of VEGF in the supernatants, the intracellular VEGF in DCs and the VEGF mRNA level of DCs were detected by ELISA, FACS and Q-PCR, respectively. Results: When DCs were co-cultured with TCM or rhVEGF for 3 hours, the levels of VEGF in the supernatants were significantly decreased, while the intracellular VEGF in DCs was increased. In addition, exogenous rhVEGF did not increase VEGF mRNA expression in DCs, suggesting that increased VEGF levels in DCs was due to up-take VEGF from supernatants. The function of DCs to take up VEGF could be abolished by pretreatment DCs with neutralizing antibody against VEGF receptor 1. Conclusion: It is the first time to show the novel function of DCs. Our results suggested that DCs might exert anti-angiogenic effect by clearance of VEGF via VEGF receptor 1. Therefore, administration of DCs may be the potential therapeutic strategy for patients with neuroblastoma.