Modulation of Immune suppressive tumor microenvironment based on inhibition of interaction between CAF and Treg in pancreatic cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07951
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: National Cancer Center Japan
• Principal Investigator: Aoki Kazunori 国立研究開発法人国立がん研究センター, 研究所, 分野長 (60270675)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 膵がん / 腫瘍微小環境 / がん関連線維芽細胞 / 制御性T細胞

Outline of Final Research Achievements

Despite constant efforts to improve treatment, the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) remains poor, with an overall survival rate of 10%. PDAC is also resistant to immune therapies including immune checkpoint inhibitors. The reason for the resistance is considered that pancreatic cancer creates a highly immunosuppressive tumor microenvironment (TME), possibly due to reactive desmoplastic stroma. In this study, we analyzed the mechanism of immune suppressive network in PDAC and elucidated that the activated cancer-associated fibroblasts induce the regulatory T cells. This interaction may be a promising target for changing the immune suppressive TME of PDAC to an anti-tumor state.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

膵がんは日本人のがん死因の４位を占め５年生存率は10％程度と低く、その理由の一つとして有効な治療法が少ないことがあげられる。免疫チェックポイント阻害剤も膵がんに対して効果を発揮しないため、新たな治療法を開発することが必要である。本研究では、膵がんの免疫抑制機構の一端を明らかとし、それに基づいて有望な治療標的を同定した。本研究成果は、将来的に免疫療法の開発に結び付く可能性があり、膵がんの治療体系に大きなインパクトがある。