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The FEBS journal

Suppression of vascular endothelial growth factor abrogates the immunosuppressive capability of murine gastric cancer cells and elicits antitumor immunity.


PMID 25041128

Abstract

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.