title: Suppression of vascular endothelial growth factor abrogates the immunosuppressive capability of murine gastric cancer cells and elicits antitumor immunity.
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.
authors.affiliation: Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.forename: Peiwu
authors.initials: P
authors.lastname: Yu
authors.forename: Dongzhu
authors.initials: D
authors.lastname: Zeng
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.forename: Xiao
authors.initials: X
authors.lastname: Lei
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
authors.forename: Yingxue
authors.initials: Y
authors.lastname: Hao
authors.forename: Huaxing
authors.initials: H
authors.lastname: Luo
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Yongjia
authors.initials: Y
authors.lastname: Tan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000187:drug effects*; D015536:Down-Regulation; D007108:Immune Tolerance / Q000502:physiology*; D051379:Mice; D009368:Neoplasm Transplantation; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D042461:Vascular Endothelial Growth Factor A
keywords: antitumor immunity; gastric cancer; immune evasion; vascular endothelial growth factor