Immune response and direct interaction of CD1a-positive dendritic cells in gallbladder cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07408
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Saga University
• Principal Investigator: Kai Keita 佐賀大学, 医学部, 准教授 (60516540)
• Co-Investigator(Kenkyū-buntansha): 菰原 義弘 熊本大学, 大学院生命科学研究部(医), 教授 (40449921) ; 田中 智和 佐賀大学, 医学部, 助教 (60781903)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 胆嚢癌 / 樹状細胞 / 単球 / CD1a / 多核巨細胞 / 腫瘍免疫

Outline of Final Research Achievements

To elucidate the mechanism of interaction between CD1a-positive dendritic cells (CD1a-DCs) and gallbladder cancer cells, monocytes were cultured and induced into CD1a-DCs and interactions with gallbladder cancer cell lines were analyzed. To clarify the significance of CD1a-DCs infiltration in the regional lymph nodes of gallbladder cancer, we analyzed the infiltration of CD1a-DCs in gallbladder cancer tissue and regional lymph nodes. As a result, following new finding was obtained: CD1a-DCs are induced by cytokines, but CD1a-DCs are also induced by cancer cells. In the presence of cancer cells and cytokines, multinucleated giant cells are induced. High-infiltration of CD1a-DCs is observed only in metastatic lymph nodes. The infiltration of CD1a-DCs in the primary tumor was significantly associated with survival in cases with lymph node metastasis

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

今回の研究成果から「血管から遊出した単球は腫瘍との直接相互作用でCD1a-DCsに分化し、リンパ節に移動することなく腫瘍局所で免疫応答を行う」という仮説が提案できる。今後CD1a-DCsを誘導する腫瘍の発現形質に焦点をあて研究を行うことで、CD1a-DCsを介した腫瘍免疫応答のメカニズムの解明、ひいては新規の免疫療法の開発に期待できる。また「癌細胞とサイトカインが存在する状況下で、単球から多核巨細胞が誘導される」という副産物的な成果が得られた。これは固形癌手術検体の病理診断時に稀に認める「リンパ節のsarcoid reaction」という現象を説明する手掛かりとなる知見である。