Exploration of tumor-promoting inflammatory immune responses and its application for cancer treatment

• Project/Area Number: 26430158
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: University of Toyama
• Principal Investigator: Hayakawa Yoshihiro 富山大学, 和漢医薬学総合研究所, 准教授 (10541956)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: がん / 免疫 / 炎症 / 転移 / 自然免疫

Outline of Final Research Achievements

In this study, we found IL-17A is a critical cue for escalating cancer cell malignancy. We further demonstrated the length of exposure to an inflammatory microenvironment could associate with acquiring greater tumorigenicity and IL-17A was critical for amplifying such local inflammation as observed in the production of IL-1βand neutrophil infiltration following the cross-talk between cancer and host stromal cells. We further determined that γδT cells expressing Vδ1 semi-invariant TCR initiate cancer-promoting inflammation by producing IL-17A in an MyD88/IL-23 dependent manner. Finally, we identified CD30 as a key molecule in the inflammatory function of Vδ1T cells and the blockade of this pathway targeted this cancer immune-escalation process. Collectively, these results reveal the importance of IL-17A-producing CD30+ Vδ1T cells in triggering inflammation and orchestrating a microenvironment leading to cancer progression.

Research Products

• [Journal Article] IL-17A-producing CD30(+) Vδ1 T cells drive inflammation-induced cancer progression. (2016)
  • Author(s): Kimura Y, Nagai N, Tsunekawa N, Sato-Matsushita M, Yoshimoto T, Cua DJ, Iwakura Y, Yagita H, Okada F, Tahara H, Saiki I, Irimura T, Hayakawa Y.
  • Journal Title: Cancer Sci. Volume: 107 Issue: 9 Pages: 1206-14
  • DOI: 10.1111/cas.13005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Targeting innate lymphocytes to regulate cancer-associated inflammation (2016)
  • Author(s): Yoshihiro Hayakawa
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-10-06
• [Presentation] 自然リンパ球をターゲットとしたがん関連炎症の制御 (2016)
  • Author(s): 早川芳弘
  • Organizer: 第25回日本がん転移学会学術集会・総会
  • Place of Presentation: 米子コンベンションセンター
  • Year and Date: 2016-07-21
  • Invited
• [Presentation] がん悪性化進展を促す炎症性免疫応答の維持機構におけるIL-17の重要 (2015)
  • Author(s): 早川 芳弘、済木 育夫、入村 達郎
  • Organizer: 日本がん転移学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-07-23
• [Presentation] Vd1 T細胞を起点とする炎症によるがん悪性化メカニズムの理解と治療への応用 (2015)
  • Author(s): 早川 芳弘
  • Organizer: がん分子標的学会
  • Place of Presentation: 松山
  • Year and Date: 2015-06-10
• [Presentation] Vδ1 T細胞を起点とする自然炎症はがん悪性化を促進する (2014)
  • Author(s): 早川芳弘, 木村好孝, 永井 直, 松下まりも, 田原秀晃, 善本隆之, 済木育夫, 入村達郎
  • Organizer: 第18回日本がん免疫学会
  • Place of Presentation: 松山
  • Year and Date: 2014-07-31 – 2014-08-01
• [Presentation] Vδ1 T細胞を起点とする自然炎症はがん悪性化を促進する (2014)
  • Author(s): 早川芳弘, 済木育夫, 入村達郎
  • Organizer: 第23回日本がん転移学会
  • Place of Presentation: 金沢
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] がん治療標的としての宿主免疫応答 (2014)
  • Author(s): 早川芳弘
  • Organizer: フォーラム富山創薬 第39回研究会
  • Place of Presentation: 富山
  • Year and Date: 2014-05-22
  • Invited
• [Book] 臨床免疫・アレルギー科 (2014)
  • Author(s): 早川芳弘
  • Total Pages: 4
  • Publisher: 科学評論社