Development of new colorectal cancer treatments through targeting the gut microbiota that influence antitumor immunity and the efficacy of cancer chemotherapies.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H05094
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: Mima Kosuke 熊本大学, 病院, 非常勤診療医師 (00546559)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 大腸癌 / 肝転移 / 腸内細菌 / Fusobacterium nucleatum / 免疫 / MDSC / TAM

Outline of Final Research Achievements

Accumulating evidence links the intestinal microbiota and colorectal carcinogenesis. Fusobacterium nucleatum (F. nucleatum) has been shown to potentiate colorectal tumor growth and inhibit antitumor immune responses. Emerging evidence demonstrates an enrichment of Fusobacterium species in colorectal cancer live metastasis (CRLM).
F. nucleatum was detected in 8 (4.4%) of 181 CRLM cases. Compared with F. nucleatum-negative cases, F. nucleatum-positive cases were significantly associated with low density of CD8+ T-cells (P =0.033), and higher density of myeloid-derived suppressor cell (P = 0.015) and tumor-associated macrophage (P = 0.027) in CRLM. Our data may have implications for preventing the formation of liver metastases from colorectal cancer through targeting intestinal microflora.

Free Research Field

消化器外科学、外科腫瘍学、腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

本邦における大腸癌の罹患率、死亡率は２０００年以降横ばいであるが依然として高く、癌種別死亡数は男性第３位、女性第１位である。大腸癌に関連した死亡の主な原因は遠隔転移であり、大腸癌の遠隔転移および再発形式として最も頻度が高い臓器が肝臓である。
本研究でFusobacterium nucleatumなどの腸内細菌が大腸癌肝転移巣における抗腫瘍免疫応答の抑制に関与している可能性があり、今後Fusobacterium nucleatumや腸内細菌を標的とした新しい大腸癌肝転移の予防および治療法の確立につながる可能性がある。