Exploring innovative therapeutic targets and biomarkers to predict the efficacy of cancer immunotherapy for colorectal cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16491
• 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: Kiyozumi Yuki 熊本大学, 大学院生命科学研究部(医), 特定研究員 (30827324)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 大腸癌 / MSI-H / 癌免疫療法 / 免疫チェックポイント阻害薬

Outline of Final Research Achievements

In order to search for biomarkers of treatment effect in colorectal cancer, 979 colorectal cancer cases including prognostic analysis of surgery and chemotherapy cases including 198 Stage IV cases in 2022 were analyzed for clinicopathological factors.
Analysis of the relationship between the number of tumor-infiltrating lymphocytes and prognosis showed that the prognosis was significantly poorer in the CD3, CD8, and FOXP3 low-expressing groups, while CD4-positive lymphocytes had a significantly poorer prognosis. Activin A gene expression was clearly correlated with prognosis.
Although high Activin A expression is associated with poor prognosis, its correlation with immunological factors is not clear.For the analysis of MSI-H cases, 256 cases were analyzed. Of the 256 cases, 30 (11.7%) were MSI-H, which is consistent with previous reports. the number of MSI-H cases does not clearly identify a biomarker. The number of MSI-H cases has not led to the identification of a clear biomarker.

Free Research Field

colorectal cacner

Academic Significance and Societal Importance of the Research Achievements

900例以上の大腸癌症例を用いて免疫学的因子を網羅的に解析し、CD3,CD8,FOXP3発現が予後不良と関連していることや、CD4リンパ球陽性であることが予後不良と相関しないことが分かった。また、様々な因子との解析の中から、Activin Aという予後不良因子を抽出し、サルコペニアとの関連の中から予後不良に関わってくるということを論文で発表した。更にMSI評価を行い、大腸癌において既報と同等の頻度でMSI-Hを認める結果が得られたことは一つのValidationになることが考えられる。こちらについては更なる症例数を重ね、免疫学的因子との関連を調査する必要がある。