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Anti-tumor effector mechanisms of activated NKT cells in the tumor microenvironment for novel NKT cell-based immunotherapy

Research Project

Project/Area Number 24592083
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Thoracic surgery
Research InstitutionChiba University

Principal Investigator

MOTOHASHI Shinichiro  千葉大学, 医学(系)研究科(研究院), 教授 (60345022)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords免疫学 / NKT細胞 / 免疫療法 / バイオマーカー
Outline of Final Research Achievements

We investigated the cellular and molecular mechanisms underlying potent anti-tumor effects of ligand activated invariant NKT cells. We established the lung cancer treatment models using severe combined immunodeficiency mouse and found out that activated iNKT cells augmented the cytotoxicity of tumor-antigen specific CD8+ T cells in vitro and in vivo. The number of CD8+ T cells and interferon-gamma production in the tumor microenvironment were increased after combination immunotherapy with CD8+ T cells and iNKT cells.
Ltb4dh gene was up-regulated in good responder cases after iNKT cell-based immunotherapy. We demonstrated that increased ltb4dh expression could overcome the tumor-derived immune suppressive effects. Therefore, it raises the possibility that the regulation of this gene could lead to the improvement of therapeutic effect of iNKT cell-based immunotherapy.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (38 results)

All 2015 2014 2013 2012

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 2 results) Presentation (27 results) (of which Invited: 8 results) Book (1 results)

  • [Journal Article] Identification of chimeric antigen receptors that mediate constitutive or inducible proliferation of T cells.2015

    • Author(s)
      Frigault, M. J., Lee, J., Basil, M., Carpenito, C., Motohashi, S., Scholler, J., Kawalekar, O. U., Guedan, S., McGettigan, S., Posey, A Jr., Ang, S., Cooper, L. J., Platt, J., Johnson, F. B., Paulos, C. M., Zhao, Y., Kalos, M., Milone, M. and June, C. H.
    • Journal Title

      Cancer Immunol. Res.

      Volume: 3(4) Issue: 4 Pages: 356-67

    • DOI

      10.1158/2326-6066.cir-14-0186

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Unique expression features of cancer-type organic anion transporting polypeptide 1B3 mRNA expression in human colon and lung cancers: potential biomarker implications.2014

    • Author(s)
      Sun, Y., Furihata, T., Ishii, S., Nagai, M., Harada, M., Shimozato, O., Kamijo, T., Motohashi, S., Yoshino, I., Kamiichi, A., Kobayashi, K. and Chiba, K.
    • Journal Title

      Clin. Transl. Med.

      Volume: 3 Issue: 1 Pages: 37-37

    • DOI

      10.1186/s40169-014-0037-y

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The polycomb protein Ezh2 regulates differentiation and plasticity of CD4+ T helper type-1 and type-2 cells.2013

    • Author(s)
      Tumes, D. J., Onodera, A., Suzuki, A., Shinoda, K., Endo, Y., Iwamura, C., Hosokawa, H., Koseki, H., Tokoyoda, K., Suzuki, Y., Motohashi, S., and Nakayama, T.
    • Journal Title

      Immunity

      Volume: 39 Issue: 5 Pages: 819-32

    • DOI

      10.1016/j.immuni.2013.09.012

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gata3/Ruvbl2 complex regulates T helper 2 cell proliferation via repression of Cdkn2c expression.2013

    • Author(s)
      Hosokawa H, Tanaka T, Kato M, Tohyama H, Hanazawa A, Tamaki Y, Hirahara K, Sakikawa I, Morita A, Nagira M, Suzuki Y, Nakayama T.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 110(46) Issue: 46 Pages: 18626-18631

    • DOI

      10.1073/pnas.1311100110

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] NKT cells as an ideal target for anti-tumor immunotherapy2013

    • Author(s)
      Fujii S, Shimizu K, Okamoto Y, Kunii N, Nakayama T, Motohashi S, Taniguchi M
    • Journal Title

      Front. Immunol

      Volume: 4 Pages: 409-409

    • DOI

      10.3389/fimmu.2013.00409

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of a new organic anion transporting polypeptide 1B3 mRNA isoform primarily expressed in human cancerous tissues and cells.2012

    • Author(s)
      Nagai, M., Furihata, T., Matsumoto, S., Ishii, S., Motohashi, S., Yoshino, I., Ugajin, M., Miyajima, A., Matsumoto, S. and Chiba, K.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 418 Issue: 4 Pages: 818-823

    • DOI

      10.1016/j.bbrc.2012.01.115

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The transcription factor Sox4 is a downstream target of signaling by the cytokine TGF-・ and suppresses TH2 differentiation2012

    • Author(s)
      Kuwahara, M., Yamashita, M., Shinoda, K., Tofukuji, S., Onodera, A., Shinnakasu, R., Motohashi, S., Hosokawa, H., Tumes, D., Iwamura, C., Lefebvre, V., and Nakayama, T.
    • Journal Title

      Nat. Immunol

      Volume: 13(8) Issue: 8 Pages: 778-786

    • DOI

      10.1038/ni.2362

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Accumulation of Activated Invariant Natural Killer T Cells in the Tumor Microenvironment after α-Galactosylceramide-Pulsed Antigen Presenting Cells.2012

    • Author(s)
      Nagato K, Motohashi S, Ishibashi F, Okita K, Yamasaki K, Moriya Y, Hoshino H, Yoshida S, Hanaoka H, Fujii SI, Taniguchi M, Yoshino I, Nakayama T.
    • Journal Title

      J Clin Immunol.

      Volume: 32 Issue: 5 Pages: 1071-81

    • DOI

      10.1007/s10875-012-9697-9

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation of memory CD4 T-cell pool size and function by natural killer T cells in vivo. 109(42) : 16992-16997 (2012).2012

    • Author(s)
      Iwamura, C., Shinoda, K., Endo, Y., Watanabe, Y., Tumes, J. D., Motohashi, S., Kawahara, K., Kinjo, Y., and Nakayama, T.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 109 Issue: 42 Pages: 16992-16997

    • DOI

      10.1073/pnas.1203494109

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Murine Schnurri-2 controls Natural Killer cell function and lymphoma development2012

    • Author(s)
      Yamashita, J., Iwamura, C., Mitsumori, K., Hosokawa, H., Sasaki, T., Takahashi, M., Tanaka, H., Kaneko, K., Hanazawa, A., Watanabe, Y., Shinoda, K., Tumes, D., Motohashi, S., Nakayama, T.
    • Journal Title

      Leuk.Lymphoma

      Volume: 53 Issue: 3 Pages: 479-486

    • DOI

      10.3109/10428194.2011.625099

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 非小細胞肺癌に対するNKT細胞特異的免疫細胞療法の開発2015

    • Author(s)
      本橋 新一郎
    • Organizer
      第12回日本免疫治療学研究会学術集会
    • Place of Presentation
      東京ガーデンパレス (東京都・文京区)
    • Year and Date
      2015-02-28
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] NKT細胞を標的とした癌免疫治療とバイオマーカー探索研究2015

    • Author(s)
      本橋 新一郎
    • Organizer
      第9回獣医アトピー・アレルギー・免疫学会シンポジウム
    • Place of Presentation
      国際ファッションセンター (東京都・墨田区)
    • Year and Date
      2015-02-01
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Antigen Specific Immunotherapy Based on Chimeric Antigen Receptor Expressing T Cells Targeted to Salivary Gland Tumor2014

    • Author(s)
      Kunii, N., Makita, Y., Ihara, F., Uchida, R., Fujikawa, A., Sakurai, D., Motohashi, S., Nakayama, T. and Okamoto, Y.
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      国立京都国際会館 (京都府・京都市)
    • Year and Date
      2014-12-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Human melanoma antigen-specific iNKT cells engineered by the TIL 1383I T cell receptor gene transfer2014

    • Author(s)
      Nagato, K., Motohashi, S., Nakayama, T., Yoshino, I. and Nishimura, M. I.
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      国立京都国際会館 (京都府・京都市)
    • Year and Date
      2014-12-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] 原発性肺癌に対するNKT細胞免疫療法におけるPD-1阻害の有用性2014

    • Author(s)
      鎌田 稔子, 鈴木 茜, 藤川 陽, 三瀬 直子, 蒔田 勇治, 吉田 成利, 鈴木 秀海, 中島 崇裕, 岩田 剛和, 吉野 一郎, 中山 俊憲, 本橋 新一郎
    • Organizer
      第55回日本肺癌学会学術集会
    • Place of Presentation
      国立京都国際会館 (京都府・京都市)
    • Year and Date
      2014-11-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] 骨髄系免疫抑制細胞の頭頸部腫瘍における検討2014

    • Author(s)
      堀中 敦史, 本橋 新一郎, 岡本 美孝
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜 (神奈川県・横浜市)
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] NKT cell-targeting immunotherapy for non-small cell lung cancer2014

    • Author(s)
      本橋 新一郎
    • Organizer
      第18回日本がん免疫学会総会
    • Place of Presentation
      ひめぎんホール (愛媛県・松山市)
    • Year and Date
      2014-08-01
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 悪性腫瘍に対するNKT細胞を標的とした免疫細胞治療2014

    • Author(s)
      本橋 新一郎
    • Organizer
      第1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 (東京都・文京区)
    • Year and Date
      2014-06-28
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 原発性肺癌患者におけるNKT細胞免疫治療とPD-1阻害療法の有用性2014

    • Author(s)
      鎌田 稔子, 本橋 新一郎, 吉田 成利, 鈴木 秀海, 中島 崇裕, 田川 哲三, 岩田 剛和, 溝渕 輝明, 吉野 一郎
    • Organizer
      第31回日本呼吸器外科学会総会
    • Place of Presentation
      ホテル日航東京 (東京都・港区)
    • Year and Date
      2014-05-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] NKT cell-targeting therapy for lung cancer and head and neck cancer.2013

    • Author(s)
      Motohashi, S., Kunii, N., Taniguchi, M., Yoshino, I., Okamoto, Y., and Nakayama, T.
    • Organizer
      7th International symposium on CD1 and NKT cells
    • Place of Presentation
      International Congress Centre(Tours,France)
    • Related Report
      2013 Research-status Report
  • [Presentation] 炭素イオン線治療後の頭頸部粘膜悪性黒色腫患者に対するaガラクトシルセラミドパルス抗原提示細胞を用いたアジュバント免疫治療に関する第I/II相臨床研究2013

    • Author(s)
      藤川陽、國井直樹、櫻井大樹、長谷川安都佐、鎌田正、溝江純悦、岡本美孝、本橋新一郎、中山俊憲
    • Organizer
      第17回日本がん免疫学会総会
    • Place of Presentation
      ANAクラウンプラザホテル宇部(山口県、宇部市)
    • Related Report
      2013 Research-status Report
  • [Presentation] NKT細胞免疫系をタ-ゲットにしたがんの免疫細胞治療ー10年間の臨床研究の成果と今後の展望ー2013

    • Author(s)
      中山俊憲、本橋新一郎、國井直樹、岡本美孝
    • Organizer
      第17回日本がん免疫学会総会
    • Place of Presentation
      ANAクラウンプラザホテル宇部(山口県、宇部市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] BCG-LM による好酸球活性化の抗腫瘍効果2013

    • Author(s)
      伊藤俊広、平原潔、本橋新一郎、矢野郁也、中山俊憲
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県、横浜市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 抗腫瘍免疫機構の最先端2013

    • Author(s)
      中山俊憲,本橋新一郎,國井直樹,岡本美孝
    • Organizer
      第66回日本胸部外科学会定期学術集会
    • Place of Presentation
      仙台国際センター(宮城県、仙台市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Phase I/II clinical study of α-galactosylceramide-pulsed antigen presenting cells as adjuvant immunotherapy for patients with head and neck mucosal malignant melanoma after carbon ion radiotherapy.2013

    • Author(s)
      Fujikawa, A., Kunii, N., Horinaka, A., Makita, Y., Uchida, R., Ihara, F., Motohashi, S., Okamoto, Y., and Nakayama, T.
    • Organizer
      第42回日本免疫学会総会学術集会
    • Place of Presentation
      幕張メッセ(千葉県、千葉市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Accumulation of activated invariant NKT cells in the tumor microenvironment after α-galactosylceramide-pulsed antigen presenting cells.2012

    • Author(s)
      Nagato, K., Motohashi, S. and Nakayama,T.
    • Organizer
      Clinical Immunology Society
    • Place of Presentation
      Swissotel(Chicago,USA)
    • Related Report
      2012 Research-status Report
  • [Presentation] Enhanced function of redirected human T cells expressing LAT that is resistant to ubiquitylation.2012

    • Author(s)
      國井直樹、本橋新一郎、長門芳、岡本美孝、中山俊憲
    • Organizer
      第16回日本がん免疫学会
    • Place of Presentation
      北海道大学学術交流会館(北海道)
    • Related Report
      2012 Research-status Report
  • [Presentation] 原発性肺癌に対するNKT細胞免疫治療後の腫瘍局所における免疫応答の解析2012

    • Author(s)
      本橋新一郎、石橋史博、長門芳、國井直樹、谷口克、吉野一郎、中山俊憲
    • Organizer
      第71回日本癌学会
    • Place of Presentation
      ロイトン札幌(北海道)
    • Related Report
      2012 Research-status Report
  • [Presentation] ユビキチン化抵抗性LATによるT細胞の機能増強2012

    • Author(s)
      國井直樹、本橋新一郎、岡本美孝、中山俊憲
    • Organizer
      第71回日本癌学会
    • Place of Presentation
      ロイトン札幌(北海道)
    • Related Report
      2012 Research-status Report
  • [Presentation] マウスSchnurri-2はNK細胞の機能とリンパ腫の発症を制御する2012

    • Author(s)
      伊藤俊広、三森国敏、本橋新一郎、中山俊憲
    • Organizer
      第71回日本癌学会
    • Place of Presentation
      ロイトン札幌(北海道)
    • Related Report
      2012 Research-status Report
  • [Presentation] 抗腫瘍免疫機構:自然免疫と獲得免疫による制御2012

    • Author(s)
      中山俊憲、本橋新一郎
    • Organizer
      第71回日本癌学会
    • Place of Presentation
      ロイトン札幌(北海道)
    • Related Report
      2012 Research-status Report
  • [Presentation] 非小細胞肺癌に対するαガラクトルシルセラミドパルス樹状細胞療法2012

    • Author(s)
      本橋新一郎
    • Organizer
      第50回日本癌治療学会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] マウス胸膜中皮腫におけるIFN-γ産生性iNKT細胞の役割2012

    • Author(s)
      田川哲三、岩田剛和、山田義人、鈴木秀海、坂入祐一、山本高義、田中教久、畑敦、豊田行英、溝渕輝明、本橋新一郎、吉田成利、Marc de Perrot、吉野一郎
    • Organizer
      第53回日本肺癌学会
    • Place of Presentation
      岡山全日空ホテル(岡山県)
    • Related Report
      2012 Research-status Report
  • [Presentation] cTlaN0M0非小細胞肺癌における葉切除と区域切除の経時的呼吸機能の比較2012

    • Author(s)
      森本淳一、溝渕輝明、畑敦、豊田行英、山本高義、田中敦久、鎌田稔子、坂入祐一、鈴木秀海、山田義人、田川哲三、岩田剛和、千代雅子、佐藤泰憲、本橋新一郎、吉田成利、吉野一郎
    • Organizer
      第53回日本肺癌学会
    • Place of Presentation
      岡山シティミュージアム(岡山県)
    • Related Report
      2012 Research-status Report
  • [Presentation] 小児悪性固形腫瘍に対するNKT細胞系を用いた新規免疫療法の開発研究2012

    • Author(s)
      菱木知郎、本橋新一郎、齋藤武、光永哲也、中田光政、照井エレナ、小松秀吾、三瀬直子、原田和明、吉田英生
    • Organizer
      第54回日本小児血液・がん学会
    • Place of Presentation
      パシフィコ横浜 (神奈川県)
    • Related Report
      2012 Research-status Report
  • [Presentation] NKT細胞を標的とした免疫細胞治療の現状と今後の展望2012

    • Author(s)
      本橋新一郎
    • Organizer
      第9回がんワクチン療法研究会
    • Place of Presentation
      筑波大学(茨城県)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Enhanced function of primary human T cells electroporated with RNA for LAT that is resistant to ubiquitylation.2012

    • Author(s)
      Kunii, N., Motohashi, S., Okamoto, Y. and Nakayama, T.
    • Organizer
      第41回日本免疫学会
    • Place of Presentation
      神戸国際展示場(兵庫県)
    • Related Report
      2012 Research-status Report
  • [Book] がんと免疫2015

    • Author(s)
      坂口 志文, 西川 博嘉, 池田 裕明, 小笠原 康悦, 本橋 新一郎, 廣田 圭司, 瀬谷 司, 中山 睿一, 河上 裕, 藤井 眞一郎, 垣見 和宏, 竹内 理, 島田 眞路, 小澤 敬也, 河本 宏, 玉田 耕治, 藤堂 具紀, 佐藤 昇志
    • Publisher
      南山堂
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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