Elucidation and control of the carcinogenic spiral that results from inflammation and immune responses

2014 Fiscal Year Final Research Report

• Project Area: Conversion of tumor-regulation vector to intercept oncogenic spiral accelerated by infection and inflammation
• Project/Area Number: 22114007
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: TANIGUCHI Tadatsugu 東京大学, 生産技術研究所, 特任教授 (50133616)
• Co-Investigator(Kenkyū-buntansha): YANAI Hideyuki 東京大学, 生産技術研究所, 特任准教授 (70431765) ; NEGISHI Hideo 東京大学, 生産技術研究所, 特任助教 (60514297)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: 発がんスパイラル / 制がんベクトル / 核酸認識システム / 炎症 / 感染

Outline of Final Research Achievements

The aim of the project was to investigate the mechanisms of inflammation and immune responses caused by self-derived molecules in the regulation of carcinogenic spiral. First, we found that the innate immune receptor Dectin-1 expressed on dendritic cells and macrophages is critical to NK-mediated killing of tumor cells that express high-level N-glycan structures. Second, we focused on HMGB1, known to cause inflammatory responses, for its role in inflammation and cancer. For this study, we first generated mice that allow conditional inactivation of the HMGB1 gene in a cell- and tissue-specific manner. We adduced evidence that intracellular HMGB1 contributes to the protection of mice from endotoxemia and bacterial infection. In addition, we also found that the loss of HMGB1 in the liver results in dramatic reduction of liver metastasis of tumor cells. Overall, these results suggest a novel direction in the control of carcinogenic spiral by the immune system.

Free Research Field

炎症免疫制御学 分子免疫学