Relationship between human microbiota and sarcopenia in colorectal cancer patients

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17623
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kumamoto University
• Principal Investigator: Sakamoto Yuki 熊本大学, 大学院生命科学研究部(医), 特定研究員 (70867192)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 大腸癌 / 肝転移 / 腸内細菌 / 腫瘍免疫 / Fusobacterium

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).
We measured the amount of F. nucleatum DNA in 181 CRLM tissues using a quantitative PCR assay. The density of CD8+ T-cells and myeloid derived suppressor cell (MDSC)s in CRLM was determined by immunohistochemical staining. F. nucleatum was detected in 8 (4.4%) of 181 CRLM cases. A higher density of CD8+ T-cells in CRLM was significantly associated with better relapse-free survival. F. nucleatum - positive cases were significantly associated with low density of CD8+ T-cells. Compared with F. nucleatum-negative cases with high CD8+ T cells infiltration, F. nucleatum-positive cases were significantly associated with higher density of MDSCs.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

これまでの研究でヒト口腔内常在菌であるFusobacterium nucleatum (F. nucleatum)が大腸癌の発育・進展を促進することが示唆され、肝転移巣にもF. nucleatumが認められることが明らかになった。今回の研究結果からF. nucleatum は大腸癌肝転移組織においても骨髄由来抑制細胞を介して細胞障害性T細胞を抑制し、予後不良に寄与していることが示唆され、この知見は腸内細菌を標的とした新たな大腸癌治療戦略の開発につながる可能性がある。