New therapeutic strategy against neutrophil in the tumor microenvironment of colon cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07196
• 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: Itatani Yoshiro 京都大学, 医学研究科, 助教 (80814029)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 大腸癌 / 腫瘍微小環境 / 好中球 / 血管新生 / マウスモデル

Outline of Final Research Achievements

In this study, we tried to reveal tumor promotive function of neutrophils in the tumor microenvironment of colon cancer, using mouse models of colon cancer. Neutrophil is one of the important host immune cells. However, it is also known that neutrophils promote tumor progression in the tumor microenvironment. It becomes an attractive therapeutic strategy to suppress only tumor promotive function of the neutrophils without affecting protective function against infection. CMS4 colon cancer shows poor prognosis, with resistance to anti-VEGF treatment. We found that neutrophils accumulated in the tumor microenvironment of CMS4 mouse colon cancer, secreting Bv8 angiogenic factor. When treating anti-Bv8 antibody in addition to anti VEGF antibody, tumor formation of CMS4 mouse colon cancer was suppressed.

Free Research Field

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Academic Significance and Societal Importance of the Research Achievements

CMS4大腸癌は予後不良で、大腸癌治療のキードラッグの抗VEGF治療に抵抗性を示すことが知られている。今回我々の研究では、CMS4大腸癌の抗VEGF治療耐性に好中球が深く関与すること、好中球由来の血管新生因子Bv8をVEGFとともに阻害することで、抗VEGF治療耐性が解除されることを、自然発生大腸癌マウスモデルを用いることで、より実臨床に近い環境で解明した。本邦において、大腸癌はがん死亡数では肺癌に次ぐ２番目の死亡数で、最新がん統計によると2019年は約5万人が大腸癌で死亡したとされる。本研究結果が臨床応用されれば、これらの患者の治療に有用である可能性がある。