Development of therapeutic strategy targeting the the molecule governing the differentiation of TAM

• Project/Area Number: 17K07222
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Nagasaki University (2018-2019); University of Shizuoka (2017)
• Principal Investigator: MURAOKA Daisuke 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (20608955)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 腫瘍局所マクロファージ / 免疫チェックポイント療法抵抗性 / 免疫チェックポイント阻害療法抵抗性 / マクロファージ

Outline of Final Research Achievements

Although cancer immunotherapies including immune checkpoint inhibitors therapy show efficacy in a part of the cancer patient, many patients are refractory to these immunotherapies. The mechanisms underlying this tumor immune resistance have not been fully elucidated but it has been considered that tumor-associated macrophages (TAMs) as a key factor correlate with this resistance. In this project, we identified the molecule governing the character of TAMs and established the therapeutic strategy for cancer targeting these molecules.

Academic Significance and Societal Importance of the Research Achievements

がん免疫療法の治療効果を向上させる為に、TAMを標的とした様々な戦略が取られてきた。しかしながら、未だにTAMの性質を制御する方法は確立されていない。本研究では、IKKがTAMの性質決定において重要な分子であることを明らかにし、その阻害が免疫チェックポイント阻害療法の有効性を向上させることを明らかにした。当研究成果は、今後のがん免疫療法の適応拡大につながる可能性がある。

Research Products

• [Journal Article] Antigen delivery targeted to tumor-associated macrophages overcomes tumor immune resistance (2019)
  • Author(s): Muraoka Daisuke、Seo Naohiro、Hayashi Tae、Tahara Yoshiro、Fujii Keisuke、Tawara Isao、Miyahara Yoshihiro、Okamori Kana、Yagita Hideo、Imoto Seiya、Yamaguchi Rui、Komura Mitsuhiro、Miyano Satoru、Goto Masahiro、Sawada Shin-ichi、Asai Akira、Ikeda Hiroaki、Akiyoshi Kazunari、Harada Naozumi、Shiku Hiroshi
  • Journal Title: Journal of Clinical Investigation Volume: 129 Issue: 3 Pages: 1278-1294
  • DOI: 10.1172/jci97642
  • NAID: 120006987781
  • Peer Reviewed / Open Access
• [Presentation] Delivery of a tumor antigen to TAMs by using a nanogel leads to eradication of tumor resistant to immune therapies (2019)
  • Author(s): Daisuke Muraoka
  • Organizer: 第78回日本癌学会学術総会
  • Invited
• [Presentation] 腫瘍局所マクロファージの抗原提示能誘発による難治性腫瘍の克服 (2019)
  • Author(s): 村岡大輔
  • Organizer: 第23回日本がん免疫学会総会
  • Invited
• [Presentation] TAMを標的とした免疫細胞治療抵抗性の克服戦略 (2019)
  • Author(s): 村岡大輔
  • Organizer: 第11回 日本血液疾患免疫療法学会学術集会
  • Invited
• [Presentation] 腫瘍の細胞性免疫応答反応性を規定するマクロファージの分化機構の解明 (2018)
  • Author(s): 村岡大輔、瀬尾尚宏、林妙、藤井啓介、池田裕明、秋吉一成、原田直純、珠玖洋
  • Organizer: 第22回日本がん免疫学会総会
• [Presentation] Immune sensitivity of tumor is governed by the mechanism for differentiation of tumor-associated macrophages (TAMs) (2018)
  • Author(s): Daisuke Muraoka, Naohiro Seo, Tae Hayashi, Keisuke Fujii, Hiroaki Ikeda, Kazunari Akiyoshi, Naozumi Harada and Hiroshi Shiku
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] 尾静脈投与ワクチンによる腫瘍局所マクロファージへの抗原送達が腫瘍環境に及ぼす影響の解析 (2017)
  • Author(s): 村岡大輔, 原田直純, 林妙, 秋吉一成, 珠玖洋
  • Organizer: 第21回日本がん免疫学会総会
• [Presentation] Induced Antigen Presentation by Tumor-Associated Macrophages Enhances Infilt ration of CD8+ T Cells with Low PD-1 Level (2017)
  • Author(s): Naozumi Harada, Daisuke Muraoka, Kazunari Akiyoshi, and Hiroshi Shiku
  • Organizer: 第76回日本癌学会学術総会