Neutrophil functions in the tumor microenvironment of colorectal cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07097
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kyoto University
• Principal Investigator: Itatain Yoshiro 京都大学, 医学研究科, 助教 (80814029)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 大腸癌 / 腫瘍微小環境 / 好中球

Outline of Final Research Achievements

Neutrophils are important host cells in terms of primary immune response to infection, but are also known to promote tumor invasion/metastasis in cancer patients. We hypothesized that controlling only the tumor-promoting ability of these bone marrow-derived cells while maintaining their infection-protective function would lead to the establishment of a treatment method with fewer side effects. We have reported chemokine-mediated tumor-stromal effects in the tumor microenvironment of colorectal cancer. In particular, the chemokine CCL15-CCR1 by bone marrow-derived cells and CXCL1/8-CXCR2 by neutrophils have been reported. To comprehensively investigate these factors, we analyzed the liver metastatic potential of colorectal cancer using CCR1 knockout mice, CXCR2 knockout mice, and CCR1-neutralizing antibodies. Furthermore, we focused on the action of neutrophil extracellular trap (NET) and analyzed the ability of NET to promote liver metastasis.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

大腸癌は本邦の癌死亡の上位を占める癌である。原発大腸にとどまる状態であれば手術による根治的治療が可能となるが、ひとたび転移を来すと根治的治療が困難となることも多い。腫瘍微小環境における骨髄由来細胞の役割を解明し、好中球や単球/マクロファージの感染症に対する一次免疫応答機能を保持しつつ腫瘍促進能のみを阻害できる可能性を見出したことは学術的な意義が大きい。これらが将来的に臨床応用されれば、癌死亡の上位をしめる大腸癌で、直接的な死因となりうる転移制御に対するあらたな治療方法となりうることの社会的意義は大きい。