Characterization of memory invariant NKT cells

• Project/Area Number: 26460583
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Fujii Shin-ichiro 国立研究開発法人理化学研究所, 統合生命医科学研究センター, チームリーダー (10392094)
• Co-Investigator(Kenkyū-buntansha): 清水 佳奈子 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 上級研究員 (20391980)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: NKT細胞 / 樹状細胞 / 記憶免疫 / 抗腫瘍免疫

Outline of Final Research Achievements

Invariant (i)NKT cells recognize a complex of the antigen-presenting MHC-like molecule CD1d and a glycolipid and play a key role at the initial immunological defense in infection and cancer. After the activation, the fate of iNKT cells toward memory has not been identified. Here we show the presence of effector memory-like KLRG1+iNKT cells in the lung. They express the distinct expression of adhesion molecules, chemokine receptors and NK receptors and can produce high amount of IFN-gamma. In addition, we identified the specific molecules, of KLRG1+ iNKT cells by RNA-seq analysis.

Research Products

• [Journal Article] In vivo dendritic cell targeting cellular vaccine induces CD4+ Tfh cell-dependent antibody against influenza virus. (2016)
  • Author(s): Yamasaki S, Shimizu K, Kometani K, Sakurai M, Kawamura M, and Fujii S*.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 35173-35173
  • DOI: 10.1038/srep35173
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Efficient regeneration of Human Vα24+ invariant NKT cells and their anti-tumor activity in vivo. (2016)
  • Author(s): Yamada D, Iyoda T, Vizcardo R, Shimizu K, Sato Y, Endo TA, Kitahara G, Okoshi M, Kobayashi M, Sakurai M, Ohara O, Taniguchi M, Koseki H, Fujii S*.
  • Journal Title: Stem Cells Volume: 34 Issue: 12 Pages: 2852-2860
  • DOI: 10.1002/stem.2465
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Systemic DC activation modulates the tumor microenvironment and shapes the long-lived tumor-specific memory mediated by CD8+ T cells. (2016)
  • Author(s): Shimizu K, Yamasaki S, Shinga J, Sato Y, Watanabe T, Ohara O, Kuzushima K, Yagita H, Komuro Y, Asakura M, and Fujii S*.
  • Journal Title: Cancer Res Volume: 76 Pages: 3756-66
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Systemic DC activation modulates the tumor microenvironment and shapes the long-lived tumor-specific memory mediated by CD8+ T cells (2016)
  • Author(s): 1.Shimizu K, Yamasaki S, Shinga J, Sato Y, Watanabe T, Ohara O, Kuzushima K, Yagita H, Komuro Y, Asakura M, and Fujii S.
  • Journal Title: Cancer Res Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Transfer of mRNA Encoding Invariant NKT Cell Receptors Imparts Glycolipid Specific Responses to T Cells and γδT Cells (2015)
  • Author(s): 3.Shimizu K, Shinga J, Yamasaki S, Kawamura M, Dörrie J, Schaft N, Sato Y, Iyoda T, Fujii S.
  • Journal Title: PLoS One Volume: 10 Issue: 6 Pages: e0131477-e0131477
  • DOI: 10.1371/journal.pone.0131477
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] KLRG1+ invariant natural killer T cells are long-lived effectors (2014)
  • Author(s): Shimizu K, Sato Y, Shinga J, Watanabe T, Endo T, Asakura M, Yamsaki S, Kawahara K, Kinjo Y, Kitamura H, Watarai H, Ishii Y, Tsuji M, Taniguchi M, Ohara O, Fujii S
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 111 Pages: 12474-124749
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Allogeneic DCG promote lung NK cell activation and antitumor effect after invariant NKT cell activation. (2014)
  • Author(s): Hasegawa H, Yamashita K, Otubo D, Fujii S, Kamigaki T, Kuroda D, Kakeji Y.
  • Journal Title: Anticancer Res Volume: 34 Pages: 3411-3417
  • Peer Reviewed
• [Journal Article] Adoptive cytotoxic T lymphocyte therapy triggers a counter-regulatory immunosuppressive mechanism via recruitment of myeloid-derived suppressor cells. (2014)
  • Author(s): Hosoi A, Matsushita H, Shimizu K, Fujii SI, Ueha S, Abe J, Kurachi M, Maekawa R, Matsushima K, Kakimi K.
  • Journal Title: Int J Cancer. Volume: 134 Issue: 8 Pages: 1810-22
  • DOI: 10.1002/ijc.28506
  • Peer Reviewed
• [Journal Article] 「自然免疫と獲得免疫の両方を活性化する新規がん細胞療法―人工アジュバントベクター細胞の開発―」 (2014)
  • Author(s): 藤井 眞一郎、清水 佳奈子
  • Journal Title: 細胞 Volume: 46 Pages: 22-26
• [Journal Article] 多発性骨髄腫に向けた人工アジュバントベクター細胞免疫治療の開発 (2014)
  • Author(s): 藤井 眞一郎
  • Journal Title: 血液フロンティア Volume: 24 Pages: 71-78
• [Presentation] 「癌に立ち向かう免疫の仕組み」 (2016)
  • Author(s): 藤井眞一郎
  • Organizer: 健康学習セミナー
  • Place of Presentation: 神奈川県民ホール 6階大会議室 （神奈川県 横浜）
  • Invited
• [Presentation] 「生体内樹状細胞を標的とした新規がんワクチン『人工アジュバントベクター細胞』の開発」 (2016)
  • Author(s): 藤井眞一郎
  • Organizer: 第5回皮膚科・免疫学合同リサーチセミナー名古屋市立大学医学部
  • Place of Presentation: 名古屋大学医学部（名古屋）
  • Invited
• [Presentation] 腫瘍免疫 ー自然免疫を利用したがんワクチンの開発・創薬への挑戦 (2016)
  • Author(s): 藤井眞一郎
  • Organizer: 獨協医科大学 免疫学特別講義
  • Place of Presentation: 獨協医科大学（栃木）
  • Invited
• [Presentation] 「Systemic DC activation modulates the tumor microenvironment and shapes the long-lived tumor-specific memory mediated by CD8+ T cells」 (2016)
  • Author(s): Fujii S
  • Organizer: IMS-JSI International Symposium on Immunology 2016
  • Place of Presentation: パシフィコ横浜（横浜）
  • Int'l Joint Research / Invited
• [Presentation] 「多機能性がんワクチン「人工アジュバントベクター細胞」の開発」 (2016)
  • Author(s): 藤井眞一郎
  • Organizer: 第20回日本がん免疫学会総会
  • Place of Presentation: 大阪国際交流センター（大阪）
  • Invited
• [Presentation] 「自然免疫系を利用したがんワクチンの開発」 (2016)
  • Author(s): 藤井眞一郎
  • Organizer: 千葉大学大学院 臨床腫瘍額持論 特別講義
  • Place of Presentation: 千葉大学大学院（千葉）
  • Invited
• [Presentation] 「自然免疫と獲得免疫の両者を賦活させる新規がん細胞ワクチン「人工アジュバントベクター細胞」の開発」 (2016)
  • Author(s): 藤井眞一郎
  • Organizer: 第12回広島肝胆膵研究会
  • Place of Presentation: ホテルグランヴィア広島（広島）
  • Invited
• [Presentation] “Development of Novel Type of Cancer Vaccine “aAVC” in RIKEN Drug Discovery and Medical Technology Platforms” (2015)
  • Author(s): Shin-ichiro Fujii
  • Organizer: The 74th Annual Meeting of The Japanese Cancer Association
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-10-08
  • Invited
• [Presentation] 「悪性リンパ腫に伴うNK細胞依存性骨髄由来抑制細胞サブセットの同定と免疫制御機構」 (2015)
  • Author(s): 藤井眞一郎
  • Organizer: 第７回血液疾患免疫療法研究会学術集会
  • Place of Presentation: 東京大学伊藤謝恩ホール（東京都）
  • Year and Date: 2015-09-26
• [Presentation] KLRG1+iNKT cells are long-lived effectors (2014)
  • Author(s): Kannko Shimizu, Yusuke Sato, Satoru, Yamasaki, Shin-ichiro Fujii
  • Organizer: 日本免疫学会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] “Immunological memory and antitumor immunity elicited by artificial adjuvant vector cells for cancer immunotherapy” (2014)
  • Author(s): Shin-ichiro Fujii
  • Organizer: 日本免疫学会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2014-12-10 – 2014-12-12
  • Invited
• [Presentation] 新規がんワクチン製剤「人工アジュバントベクター細胞」の開発 (2014)
  • Author(s): 藤井眞一郎
  • Organizer: 第2回細胞加工・細胞治療研究会
  • Place of Presentation: 東京大学医学部附属病院
  • Year and Date: 2014-12-06
  • Invited
• [Presentation] The functional analyses of induced pluripotent stem cell (iPSCs)-derived human invariant NKT cells. (2014)
  • Author(s): 藤井眞一郎、伊豫田智則、山田大輔、清水佳奈子、寺川三貴、石川文彦、谷口克、古関明彦.
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] NKT 細胞による生体内樹状細胞活性化を利用した新規がんワクチン「人工アジュバントベクター細胞」の開発 (2014)
  • Author(s): 藤井眞一郎
  • Organizer: 第6回血液疾患免疫療法研究会学術集会
  • Place of Presentation: 京都大学し芝蘭会館山内ホール
  • Year and Date: 2014-09-06
• [Presentation] Development of artificial adjuvant vector cells as a multifunctional cancer vaccine (2014)
  • Author(s): 藤井眞一郎、清水佳奈子、信賀順、山崎哲、佐藤悠輔
  • Organizer: 第18回日本がん免疫学会総会
  • Place of Presentation: 松山ひめぎんホール
  • Year and Date: 2014-07-31 – 2014-08-01
• [Presentation] Development of a novel type of cancer vaccine linking innate and adaptive immunity (2014)
  • Author(s): Shin-ichiro Fujii
  • Organizer: The 22nd International Symposium on Molecular Cell biology of Macrophage
  • Place of Presentation: 神戸商工会議所
  • Year and Date: 2014-06-02 – 2014-06-03
  • Invited
• [Book] 「多機能性がんワクチン細胞製剤「人工アジュバントベクター細胞」 (2016)
  • Author(s): 藤井 眞一郎
  • Publisher: 実験医学
• [Book] 「樹状細胞の種類と作用」 (2016)
  • Author(s): 藤井 眞一郎
  • Total Pages: 9
  • Publisher: 分子リウマチ治療
• [Book] 医学のあゆみ (2015)
  • Author(s): 藤井 眞一郎
  • Total Pages: 5
  • Publisher: 医歯薬出版株式会社
• [Book] がんと免疫 (2015)
  • Author(s): 藤井眞一郎
  • Total Pages: 5
  • Publisher: 南山堂
• [Book] Inflammation and Immunity in Cancer (2015)
  • Author(s): Fujii S, Shinga J, Yamsaki S, Sato Y, Asakura M, Shimizu K
  • Total Pages: 6
  • Publisher: Springer Japan KK
• [Remarks] プレスリリース 記憶免疫機能を持つナチュラルキラーT（NKT）細胞を発見
  • URL: http://www.riken.jp/pr/press/2014/20140819_2