Vascular Endothelial Growth Factor and Dendritic Cells in Human Squamous Cell Carcinoma of the Oral Cavity

Abstract

Dendritic cells (DCs) play an important role in the host immune defense against tumors, and there is an inverse correlation between DC density and the expression of vascular endothelial growth factor (VEGF). However, the relationship between VEGF expression in tumors and infiltration of CD1a⁺ or CD83⁺ DCs, which express the VEGF receptor (VEGFR), remains unclear. Therefore, in vivo and in vitro studies were conducted to investigate the relationship between VEGF expression and DC subsets in oral squamous cell carcinomas (OSCCs). Strong VEGF expression was detected in cancer tissues from patients with regional lymph node metastasis (PN⁺ cases). In these tissues, the VEGF expression correlated inversely with the number of CD1a⁺ DCs, but positively with the number of CD83⁺ DCs. Large amounts of VEGF were secreted by OSCCs cell lines, and their culture supernatants significantly inhibited the production of differentiated CD1a⁺ DCs from peripheral blood mononuclear cells (PBMCs), whereas differentiated CD83⁺ DCs were increased. VEGFR-1 and -2 were detected in a few PBMCs and CD1a⁺ DCs. Furthermore, CD1a mRNA disappeared when recombinant human VEGF165 (rhVEGF₁₆₅) was added to CD1a⁺ DCs, while CD83 mRNA increased. These results suggest that, in OSCCs, secreted VEGF might promote escape from tumor immunity by inhibiting the differentiation of CD1a⁺ DCs from progenitor cells and increasing the levels of dysfunctional CD83⁺ DCs.