Role of trogositosis in tumor immune escape

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08649
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Jichi Medical University
• Principal Investigator: Saito Shin 自治医科大学, 医学部, 准教授 (60382909)
• Co-Investigator(Kenkyū-buntansha): 北山 丈二 自治医科大学, 医学部, 教授 (20251308) ; 山口 博紀 自治医科大学, 医学部, 教授 (20376445) ; 佐田友 藍 自治医科大学, 医学部, 助教 (40528585) ; 相澤 健一 自治医科大学, 医学部, 准教授 (70436484) ; 宮戸 秀世 自治医科大学, 医学部, 准教授 (90813163)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: トルゴサイトーシス / がん転移 / リンパ球 / 接着分子

Outline of Final Research Achievements

We investigated the significance of membrane fragment transfer after contact (trogocytosis) between cancer cells and immune cells in vitro, based on the hypothesis that the phenomenon may affect the metastatic potential of cancer. When the cell membrane of T cells was fluorescently stained with PKH26 and co-cultured with cancer cells, a part of cancer cells turned out to be PKH26 positive. We investigated the expression of immune synapse molecules in cancer cells after co-culture with T cells. A part of cancer cells expressed CD11a and this expression was enhanced by activation of T cells. Furthermore, co-culture with activated T cells enhanced the ability of adhesion of cancer cells to vascular endothelium (HUVEC) in a CD11a-dependent manner. These evidences suggest that cancer cells may acquire CD11a from T cells through trogocytosis, thereby enhancing their metastatic potential.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

今回の研究により、癌細胞は血液中でTリンパ球による障害を免れるとtrogocytosisによりCD11aを獲得することで、標的臓器の血管内皮への接着性が亢進し、血行性転移能が増強する可能性があると考えられた。癌の転移へのトロゴサイトーシスの関与を示した報告はこれまでになく、新たな癌の転移メカニズムを示した点で今回の研究は学術的意義が高いと考えられる。