The mechanisms underlying immune evasion by gastric cancer have not been well described due to a lack of gastric tumor models in immunocompetent mice. In the current study, we found that supernatants from MFC cells, a murine gastric cancer line, inhibited the lipopolysaccharide (LPS) induced maturation and cross-presentation of bone-marrow-derived dendritic cells (BMDCs). Moreover, MFC tumor-derived factors markedly altered the cytokine profiles of BMDCs, leading to a trend of increased levels of interleukin 4 (IL4), IL6, IL23 and transforming growth factor β, as well as decreased levels of tumor necrosis factor α. qPCR and ELISA revealed that MFC cells expressed a high level of vascular endothelial growth factor (VEGF). Downregulating VEGF expression abrogated the inhibitory effect of MFC-derived factors on the maturation and cross-presentation of BMDCs. In addition, VEGF knockdown greatly impaired the tumorigenicity of MFC cells in immunocompetent mice. Compared with parental MFC tumors, VEGF-low MFC tumors grew much more slowly and the survival of tumor-inoculated mice was significantly improved. More importantly, mice rejecting inoculated VEGF-low MFC tumor cells gained resistance to re-challenged parental tumors, which was attributed to an antitumor immunity response against parental MFC tumors. These results reveal an immunosuppressive role for VEGF in murine gastric cancer.
Keywords: antitumor immunity; gastric cancer; immune evasion; vascular endothelial growth factor.
© 2014 FEBS.