Type I IFN-producing myeloid cells as a cell preparation for lung caner

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10806
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: National Cancer Center Japan
• Principal Investigator: Fukuda Kyoko (張エイ) 国立研究開発法人国立がん研究センター, 先端医療開発センター, 研究員 (00643719)
• Co-Investigator(Kenkyū-buntansha): 千住 覚 熊本大学, 大学院生命科学研究部(医), 准教授 (50274709)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 外科 / がん / 免疫 / インターフェロン / 人工多能性幹細胞 / がん免疫療法

Outline of Final Research Achievements

Type I interferons (IFNs) play important roles in antitumor immunity. We generated
IFN-α-producing cells by genetically engineering induced pluripotent stem cell (iPSC)-derived proliferating myeloid cells (iPSC-pMCs). Local administration of IFN-α-producing iPSC-pMCs (IFN-α-iPSC-pMCs) alters the tumor microenvironment and propagates the molecular signature associated with type I IFN. The gene-modified cell actively influences host XCR1+ dendritic cells to enhance CD8+ T cell priming, resulting in CXCR3-dependent and STING-IRF3 pathway-independent systemic tumor control. Administration of IFN-α-iPSC-pMCs in combination with immune checkpoint blockade overcomes resistance to single-treatment modalities and generates long-lasting antitumor immunity. These preclinical data suggest that IFN-α-iPSC-pMCs might constitute effective immune-stimulating agents for cancer that are refractory to checkpoint blockade.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

IFN-α-pMCの抗腫瘍効果の詳細なメカニズムを明らかにしたところに学術的意義を有する。特にIFN-α-pMCによって産生される1型IFNの作用点を決定した点は注目に値する。また、免疫チェックポイント阻害剤抵抗性のがんを克服するための新たな医療技術が提案され社会的意義は大きい。