Cancer stem cell targeting therapy for colorectal cancer by regulating a factor involved in the control of immunogenicity

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16712
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kyoto University
• Principal Investigator: Nakanishi Yuki 京都大学, 医学研究科, 特定助教 (40838679)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 大腸癌 / 癌幹細胞 / 癌免疫療法

Outline of Final Research Achievements

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Immunotherapy could be a viable option for patients with cancers; however, most CRCs (MSS CRCs), except those with MSI-high CRCs, respond poorly to immunotherapy. Through this project, we found the unresponsiveness of MSS CRC is caused, at least in part, by low immunogenicity induced by cancer stem cells. By targeting this mechanism, the new immunotherapy for CRC would be developed. We believe our proposal is highly significant and of great impact as it harbors the potential to fill a major gap in the field of immunotherapy for cancers which are resistant to current immunotherapy.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

癌免疫療法は大腸癌に対しては、ごく少数のマイクロサテライト不安定性（MSI-high）癌を除き、大多数をしめるマイクロサテライト安定性（MSS）癌には有効性が認められていない。本研究を通じて、MSS大腸癌における免疫治療抵抗性が形成される機序解明のための基礎的知見を得ることができた。今後、同機構を標的とすることにより、大腸癌の免疫治療抵抗性を克服する新規癌免疫療法開発につながる可能性がある。また、癌幹細胞の存在が示唆される他の多くの癌種に対しても、あてはまる普遍性を持つ研究であり、本研究の知見が癌種一般に対する治療成績向上につながることが期待される。