关键词: 树突细胞, 免疫治疗, 结直肠癌, Wnt通路, IL?1β

Abstract: ［Abstract］ Objective Wnt pathway activation exists in most colorectal cancer. Basic research has found that Wnt pathway can affect tumor immunity， but its role in colon cancer is unknown. This study focused on the effects of Wnt pathway activation on the immune microenvironment of colon cancer in order to find new targets for immunotherapy of colorectal cancer. Methods Immunofluorescence was used to verify the Wnt pathway status of SW480 and NCM460.The expressions of IL?1β in Wnt?activated colon cancer cell line SW480 and normal intestinal epithelial cell line NCM460 were compared by qPCR and Western blot. Human peripheral blood mononuclear cells were isolated and induced to form immature dendritic cells （iDC） by colony stimulating factor （GM?CSF） and IL?4， and then stimulated to induce mature dendritic cells （mDC） by using IL?1β. Expression of mature molecules on the surface of mDC cells was detected by flow cytometry. Results SW480 cells expressed beta?catenin in the nucleus， suggesting activation of the Wnt pathway. IL?1β mRNA and protein expressions increased after treatment with SW480 using Wnt pathway inhibitor （ICG?001） and increased with increasing concentration， IL?1β mRNA and protein expressions were lower in the NCM460 treated with wnt pathway activator （Licl）， and decreased with increasing concentration， and the expressions of IL?1β protein were negatively correlated with the expressions of non?phosphorylated β?catenin protein. IL?1β can promote iDC maturation， and the expression rates of HLA?DR and CD86 in IL?1β 50 ng/ml group were （69±3.62）% and （84.3±4.7）%， respectively， and the expression was significantly up?regulated compared to the RPMI group and the TNF?a 10 ng/ml group （P<0.001）. Conclusion Wnt pathway activation in colorectal cancer may inhibit the maturation of DC in tumor microenvironmentby reducing the expression of IL?1β.

Key words: wnt pathway, colorectal cancer, dendritic cells, immunity therapy, IL?1β