Mechanisms of the egression of low density granulocytes from bone marrow in patients with advancer cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16543
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Jichi Medical University
• Principal Investigator: Kumagai Yuko 自治医科大学, 医学部, 助教 (30625554)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 大腸癌 / 再発 / 低比重好中球 / 好中球細胞外トラップ / 無再発生存期間 / 手術侵襲

Outline of Final Research Achievements

In patients undergoing radical colectomy, the number of CD66b(+) low density neutrophils (LDN) significantly increased in CD45(+) leukocytes immediately after surgery, and recurrence-free survival was significantly shorter in patients with high LDN levels, making them an independent prognostic factor. In patients with stage III disease, adjuvant chemotherapy significantly improved RFS in patients with high LDN levels, but no difference in prognosis was observed in patients with low LDN levels. These LDN produced large amounts of neutrophil extracellular traps (NETs) after short-term culture and efficiently captured tumor cells in vitro. LDN are induced in the circulation by surgical stress early after colorectal cancer surgery and are thought to be associated with recurrence through the production of NETs.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

手術前後の末梢血中の低比重好中球（LDN）の表現型を特定し、アポトーシスを起こしにくいという新規知見を得ることができた。また、100例を超える臨床検体用いて、術後LDNの割合が再発を予測する新たなバイオマーカーとなりうることを示唆する結果が得られた。また、ステージ III の大腸癌患者において、補助化学療法はLDN 高値群の予後を有意に改善させたが、LDN低値群では予後に差を認めなかったことから、大腸癌術後の補助化学療法の適応に関する示唆を与えることができた点で社会的意義が大きい。