Abstract 793: Direct inhibitory effects of gastric cancer against dendritic cells

Abstract

Abstract Dendritic cells (DC) are professional antigen-presenting cells which englobe tumor-associated antigens and activated cytotoxic T lymphocytes. Otherwise, in recent studies, it has been demonstrated that immature DC such as tolerogenic DC were associated with suppression of anti-tumor immune response. The immature DC infiltrating tumor microenvironment promote tumor growth and angiogenesis in lung cancer, ovarian cancer and breast cancer. Various cytokines secreted by pancreatic cancer suppress the maturation of DC. CD4+CD25+ regulatory T cells inhibit the anti-tumor response against colon cancer. Although it has been suggested that regulatory T cells and tolerogenic DC might be associated with the immunosuppressive mechanism in cancer patients, it has not been revealed yet. In this study, we examined direct inhibitory effects of gastric cancer against DC. We designed to assess the effects of tumor-associated cytokines secreted by gastric cancer cells on DC maturation and function. Next, after culturing DC in the medium with supernatant of gastric cancer and protein-bound polysaccharide K (PSK), we examined cytokines of interleukin-10 (IL-10) of DC, which considered immunosuppressive cytokine. Various gastric cancer cell lines, included scirrhous gastric cancer secreted immunosuppressive cytokines, such as TGF-β, IL-10 and VEGF. The expression of HLA-DR as positive costimulatory molecule of DC was decreased, and that of programmed death-ligand 2 (PD-L2), as negative costimulatory molecule was increased in the medium included supernatant of gastric cancer cells. IL-10 secreted in the supernatant of DC cultured with supernatant of gastric cancer cells was increased, and inhibited by co-culturing with PSK. In conclusion, the maturation of DC was inhibited by various immunosuppressive cytokines secreted by gastric cancer cells and tolerogenic DC were induced. These results suggest that tolerogenic DC infiltrates around tumors, inhibits immune response against tumors and promote growth of tumor in gastric cancer patients. In addition, PSK might suppress the effects of tolerogenic DC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 793. doi:10.1158/1538-7445.AM2011-793