Sialoglycan facilitate cancer escape from immunosurveillance via sialic acid-binding Siglec-7 on NK cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860320
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Nagoya University
• Principal Investigator: Hashimoto Noboru 名古屋大学, 医学(系)研究科(研究院), 研究機関研究員 (90712365)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 糖鎖 / 癌 / 免疫 / 免疫監視機構 / 質量分析 / シアル酸

Outline of Final Research Achievements

Siglec-7 is an inhibitory receptor expressed on NK cells and monocytes and transduces inhibitory signals into immune cells by binding to its ligands. Although a few ligands have been reported, specificity of Siglec-7-recognized structures has not been clarified. To solve this issue, we established several sialyltransferase-transfectants that showed definite binding of Siglec-7-Fc using a human colon cancer cell line. By using the transfectants, we clarified o-glycan is a new ligand of Siglec-7. While NK cells showed high cytotoxic activity toward the parent cells, reduced cytotoxicity was observed for the transfectants. In addition, ITIM of Siglec-7 was strongly phosphorylated in the transfectants. As for the transfectants, Siglec-7-binding enhanced cell migration. Taken together, we suggest that interaction between Siglec-7 and O-glycan enable cancer cells to escape from immunosurveillance by suppression of immune cells and enhancement of cancer malignancy.

Free Research Field

生化学、糖鎖生物学