Development of immune checkpoint therapy for metastatic colorectal cancer by targeting MUC1-C

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09032
• 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: Osaka University
• Principal Investigator: Hiraki Masayuki 大阪大学, 大学院医学系研究科, 招へい教員 (80621036)
• Co-Investigator(Kenkyū-buntansha): 山本 浩文 大阪大学, 大学院医学系研究科, 教授 (30322184)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: MUC1 / PD-L1 / 大腸癌

Outline of Final Research Achievements

Immune checkpoint inhibitors are used for many types of cancers, including colorectal cancer. However, the anti-PD-1 therapy for metastatic colorectal cancer is limited to the MSI-High subtype, which accounts for about 4% of all cases. Therefore, further study is required to expand the application of immune checkpoint inhibitors. It is known that MUC1 is highly expressed in breast and lung cancers, and we previously reported that knockdown of MUC1 suppressed PD-L1 expression and induced cell death in subcutaneous xenograft model. In this study, we investigated whether a similar mechanism exists in colorectal cancer which also highly expresses MUC1. We found that MUC1 knockdown decreased PD-L1 expression in colorectal cancer cell lines. When SK-CO1 cells were treated with MUC1-siRNA, targeted molecules of PD-L1 were revealed through IPA comprehensive analysis.

Free Research Field

消化器外科、腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害剤は様々な癌種に適応が拡大されており、成果を挙げているが、転移性大腸癌においては適応が全体の約4%であるMSI-Highのサブタイプに限られるなど、未だ治療効果は広くは期待できないのが現状であり、適応拡大に繋がる研究が望まれている。本研究成果は我々がこれまで明らかにしてきた乳癌や肺癌のみならず、大腸癌においてもMUC1分子を標的とすることによって、抗PD-L1抗体による治療効果を改善させることができる可能性を示唆するものであり、学術的、社会的意義は大きい。