Genetic background factors and local cancer microenvironmental factors determining tumor immune response in colorectal cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08649
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyushu University
• Principal Investigator: Kuroda Yosuke 九州大学, 大学病院, 特別教員 (10779995)
• Co-Investigator(Kenkyū-buntansha): 三森 功士 九州大学, 大学病院, 教授 (50322748)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 腫瘍免疫応答 / コピー数変異 / TCRレパートリー / 腫瘍抗原 / 大腸がん再発

Outline of Final Research Achievements

The presence or absence of recurrence of colorectal cancer is thought to be due to differences in tumor immune responses in the primary tumor. We performed multi-region WES on 10 cases of early stage (stage I or II) colorectal tumors that recurred postoperatively. The results showed that arm-level CNAs (multiplicity) in colorectal cancer cases were significantly more common in primary tumors of recurrence-positive cases than in non-recurrent primary tumors (p < 2.2e-16), and that there was an inverse correlation between the number of SNVs and arm-level CANs (chromosomes 7p, 7q, 20p, and 20q). We found an inverse correlation between the number of SNVs and arm-level CNAs (chromosomes 7p, 7q, 20p, and 20q) in 409 TCGA colorectal cancer cases. CYT was also lower in recurrence-positive (n = 40) compared to primary tumors (n = 232) and recurrence-negative (n = 232). Pre-metastatic sites before the initiation of the metastasis can prevent cancer metastasis in the future.

Free Research Field

外科

Academic Significance and Societal Importance of the Research Achievements

われわれはコピー数異常（CNA）が、原発巣における早期から進行した腫瘍へのがん進化を促進する最も重要な選択圧であることを明らかにした。進行がんにおける中立進化の過程では、がん細胞のネオアンチゲン（NAG）の減少と細胞傷害性T細胞のTCRレパトア多様性が、クローナルなCNAやいくつかのドライバー変異とともに、原発部位から再発部位への術後再発発症を規定していた。本助成をいただき明らかにした結果に基づき、転移プロセスの開始前に、転移前の部位でCTLを活性化することは、今後がんの転移を防ぐことが可能になることが期待され、医療費逓減が求められている今日、社会的意義は大きい。