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Analysis of brain specific differentiation and maturation of tumor-infiltrating dendritic cells in glioma

Research Project

Project/Area Number 18390393
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionGifu University

Principal Investigator

SAIO Masanao  Gifu University, 大学院・医学系研究科, 准教授 (40242721)

Co-Investigator(Kenkyū-buntansha) TAKAMI Tsuyoshi  岐阜大学, 大学院・医学系研究科, 教授 (70136943)
OHE Naoyuki  岐阜大学, 大学院・医学系研究科, 講師 (60362159)
Co-Investigator(Renkei-kenkyūsha) ALAN B Frey  米国ニューヨーク大学, 細胞生物学講座, 准教授
ROZA Adany  ハンガリーデブレッツェン大学, 予防医学講座, 教授
MARGIT Balazs  ハンガリーデブレッツェン大学, 予防医学講座, 教授
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥2,280,000)
Fiscal Year 2008: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2007: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2006: ¥7,800,000 (Direct Cost: ¥7,800,000)
Keywords腫瘍内浸潤樹状細胞 / マクロファージ / 単球 / 骨髄球由来抑制細胞 / 腫瘍内浸潤マクロファージ
Research Abstract

単球, マクロファージとともに広義に樹状細胞を含む概念である腫瘍内浸潤食細胞系(腫瘍内MPC)は, その大半が単球マクロファージに分類され, 表面抗原上樹状細胞に分類できる細胞は少ないことが分かった。また, 最近報告されている骨髄球由来抑制細胞(MDSC)との異同についての検討では,腫瘍内MPCが, 強いT細胞増殖抑制能(アポトーシス誘導能)があり, 表面抗原でもCD11b陽性Gr-1陽性という定義に当てはまるため, 広義のMDSCの定義にも当てはまる可能性があったが, 細かく細胞を検討した結果, 7割ほどは既にマクロファージへ分化しており, マクロファージとしての抗腫瘍活性もT細胞抑制機能と同時に併せ持つことが分かった。他方, マクロファージへ分化していない単球の特性を維持している段階の腫瘍内MPCには抗腫瘍免疫誘導作用があり, 皮下にその細胞を樹状細胞ワクチンとして接種してから頭蓋内に腫瘍を接種すると生存日数が延長することが分かった。つまり,腫瘍内に浸潤して間もない単球分画には単球由来樹状細胞へと分化する能力があることが示唆された。ただし, 皮下, 頭蓋内, 肝内で腫瘍内MPCを検討した結果では, 腫瘍の接種部位が異なっても腫瘍内MPCの特徴は明らかな差異が見られなかったが,腫瘍の種類が違うと,差異がみられた。従って腫瘍の発育する環境というよりは, 腫瘍から産生される因子による方が,腫瘍内MPCの分化には強く影響することが分かった。そこで, 腫瘍の微小環境を免疫治療によって変化させてみた場合, 対照群では大きく腫瘍内MPCの分化成熟に影響を及ぼしていなかったCD4陽性細胞が, 免疫治療モデルでは, 腫瘍内浸潤MPCの分化成熟に影響していることがわかった。さらに検討をすると, 免疫治療モデルでは, 腫瘍内浸潤CD4陽性T細胞の性格が,Th2よりもTh1優位になっているからであることが分かった。

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (35 results)

All 2009 2008 2007

All Journal Article (8 results) (of which Peer Reviewed: 6 results) Presentation (27 results)

  • [Journal Article] Skewing the Th cell phenotype toward Th1 alters the maturation of tumor-infiltrating mononuclear phagocytes2008

    • Author(s)
      Nonaka, K., Saio, M., Suwa, T., Frey, A. B., Umemura, N., Imai, H., Ouyang, G. F., Osada, S., Balazs, M., Adany, R., Kawaguchi, Y., Yoshida, K., and Takami, T.
    • Journal Title

      J Leukoc Biol 84

      Pages: 679-688

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tumor-infiltrating myeloid-derived suppressor cells are pleiotropic inflamed monocytes/macrophages that bear M1- and M2-type characteristics2008

    • Author(s)
      Umemura, N., Saio, M., Suwa, T., Kitoh, Y., Bai, J., Nonaka, K., Ouyang, G. F., Okada, M., Balazs, M., Adany, R., Shibata, T., and Takami, T.
    • Journal Title

      J Leukoc Biol 83

      Pages: 1136-1144

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tumor-infiltrating myeloid-derived suppressor cells are pleiotropic-inflamed monocytes/macrophages that bear M1- and M2-type characteristics2008

    • Author(s)
      Umemura, N., Saio, M., Suwa, T, Kitoh, Y., Bai, J., Nonaka, K., Ouyang, G. F., Okada, M., Balazs, M., Adany, R., Shibata, T., Takami, T.
    • Journal Title

      J Leukoc Biol 83

      Pages: 1136-1144

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Skewing the Th cell phenotype toward Th1 alters the maturation of tumor-infiltrating mononuclear phagocytes2008

    • Author(s)
      Nonaka, K., Saio, M., Suwa, T., Frey, A. B., Umemura, N., Imai, H., Ouyang, G. F., Osada, S., B alazs, M., Adany, R., Kawaguchi, Y., Yoshida, K., Takami, T.
    • Journal Title

      J Leukoc Biol 84

      Pages: 679-688

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TNF expressed by tumor-associated macrophages, but not microglia2007

    • Author(s)
      Nakagawa, J., Saio, M., Tamakawa, N., Suwa, T., Frey, A. B., Nonaka, K., Umemura, N., Imai, H., Ouyang, G. F., Ohe, N., Yano, H., Yoshimura, S., Iwama, T., and Takami, T.
    • Journal Title

      can eliminate glioma. Int J Oncol 30

      Pages: 803-811

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Depletion of CD4+CD25+ regulatory T cells enhances interleukin 2 induced antitumor immunity in a mouse model of colon adenocarcinoma2007

    • Author(s)
      Imai, H., Saio, M., Nonaka, K., Suwa, T., Umemura, N., Ouyang, G. F., Nakagawa, J., Tomita, H., Osada, S., Sugiyama, Y., Adachi, Y., and Takami, T.
    • Journal Title

      Cancer Sci. 98

      Pages: 416-423

    • NAID

      10019481961

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] TNF expressed by tumor-associated mocrophages, but not microglia, can eliminate glioma.2007

    • Author(s)
      Nakagawa J, Saito M, Tamakawa N, Suwa T, Frey AB, Nonaka K, Umemura N, Imai H, Ouyang GF, Ohe N, Yano H, Yoshimura S, Iwama T, Takami T
    • Journal Title

      Int J Oncol 30

      Pages: 803-811

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Depletion of CD4(+)CD25(+) regulatory T cells enhances interleukin-2-induced antitumor immunity in a mouse model of colon adenocarcinoma.20072007

    • Author(s)
      Imai H, Saito M, Nonaka K, Suwa T, Umemura N, Ouyang GF, Nakagawa J, Tomita H, Osada S, Sugiyama Y, Adachi Y, Takami T
    • Journal Title

      Cancer Sci 98

      Pages: 416-423

    • Related Report
      2006 Annual Research Report
  • [Presentation] 腫瘍由来因子だけでは骨髄球系細胞をMDSCへ分化させることはできない2009

    • Author(s)
      鬼頭勇輔, 齊尾征直, 白俊丞, 包麗紅, 高見剛
    • Organizer
      第98回日本病理学会総会
    • Place of Presentation
      京都
    • Year and Date
      2009-05-03
    • Related Report
      2008 Final Research Report
  • [Presentation] 腫瘍内浸潤単核食細胞の大半には腫瘍免疫誘導能は無いが,低比重分画に強い免疫誘導能がある2009

    • Author(s)
      白俊丞, 齊尾征直, 鬼頭勇輔, 包麗紅, 高見剛
    • Organizer
      第98回日本病理学会総会
    • Place of Presentation
      京都
    • Year and Date
      2009-05-03
    • Related Report
      2008 Final Research Report
  • [Presentation] 腫瘍内浸潤単核食細胞系は炎症性単球とマクロファージ主体で樹状細胞にはほとんど分類されない2009

    • Author(s)
      齊尾征直, 鬼頭勇輔, 白俊丞, 包麗紅, 高見剛
    • Organizer
      第98回日本病理学会総会
    • Place of Presentation
      京都
    • Year and Date
      2009-05-03
    • Related Report
      2008 Final Research Report
  • [Presentation] The main source of TGF-b in the tumor microenvironment are the tumor-infiltrating CD11b+ cells2008

    • Author(s)
      Umemura, N., Saio, M., Nonaka, K., Suwa, T., Shibata, T., and Takami, T.
    • Organizer
      41th Annual meeting of the Society for Leukocyte Biology
    • Place of Presentation
      Denver, USA
    • Year and Date
      2008-11-07
    • Related Report
      2008 Final Research Report
  • [Presentation] The main source of TGF-b in the tumor microenvironment are the tumor-infiltrating CD11b+ cells.2008

    • Author(s)
      Umemura, N., Saio, M., Nonaka, K., Suwa, T., Shibata, T., Takami, T.
    • Organizer
      41th Annual meeting of the Society for Leukocyte Biology
    • Place of Presentation
      Denver, USA
    • Year and Date
      2008-11-07
    • Related Report
      2008 Annual Research Report
  • [Presentation] Tumor-derived factor alone could not induce myeloid-derived suppressor cell phenotype2008

    • Author(s)
      Kito, Y., Saio, M., Umemura, N., and Takami, T.
    • Organizer
      41th Annual meeting of the Society for Leukocyte Biology
    • Place of Presentation
      Denver, USA
    • Year and Date
      2008-11-06
    • Related Report
      2008 Final Research Report
  • [Presentation] Tumor-infiltrating mononuclear phagocytes are not immature myeloid cells nor immature dendritic cells rather MHC class II+ mature phenotype with immunosuppressive property2008

    • Author(s)
      Saio, M., Bai, J., Umemura, N., Nonaka, K., Okada, M., Kito, Y., Suwa, T., Ohe, N., and Takami, T.
    • Organizer
      41th Annual meeting of the Society for Leukocyte Biology
    • Place of Presentation
      Denver, USA
    • Year and Date
      2008-11-06
    • Related Report
      2008 Final Research Report
  • [Presentation] Tumor-derived factor alone could not induce myeloid-derived suppressor cell phenotype.2008

    • Author(s)
      Kito, Y., Saio, M., Umemura, N., Takami, T.
    • Organizer
      41th Annual meeting of the Society for Leukocyte Biology
    • Place of Presentation
      Denver, USA
    • Year and Date
      2008-11-06
    • Related Report
      2008 Annual Research Report
  • [Presentation] Tumor-infiltrating mononuclear phagocytes are not immature myeloid cells nor immature dendritic cells rather MHC class 11+ mature phenotype with immunosuppressive property.2008

    • Author(s)
      Saio, M., Bai, J., Umemura, N., Nonaka, K., Okada, M., Kito, Y., Suwa, T., Ohe, N., Takami, T.
    • Organizer
      41th Annual meeting of the Society for Leukocyte Biology
    • Place of Presentation
      Denver, USA
    • Year and Date
      2008-11-06
    • Related Report
      2008 Annual Research Report
  • [Presentation] Tumor-infiltrating mononuclear phagocytes mature into macrophages and few are categolized into conventional or plasmacytoid dendritic cells2008

    • Author(s)
      Saio, M., Okada, M., Bai, J., Kito, Y., Nonaka, K., Umemura, N., Suwa, T., Ohe, N., and Takami, T.
    • Organizer
      The 10th International Symposium on Dendritic cells
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2008-10-03
    • Related Report
      2008 Final Research Report
  • [Presentation] Tumor-infiltrating CD11b+cells have function of myeloid derived suppressor cells2008

    • Author(s)
      Umemura, N., Saio, M., Nonaka, K., Suwa, T., Shibata, T., and Takami, T.
    • Organizer
      The 10th International Symposium on Dendritic cells
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2008-10-03
    • Related Report
      2008 Final Research Report
  • [Presentation] Tumor-infiltrating mononuclear phagocytes mature into macrophages and few are categolized into conventional or plasmacytoid dendritic cells2008

    • Author(s)
      Saio, M., Okada, M., Bai, J., Kito, Y., Nonaka, K., Umemura, N., Suwa, T., Ohe, N., Takami, T.
    • Organizer
      The 10th Interbational Symposium on Dendritic cells
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2008-10-03
    • Related Report
      2008 Annual Research Report
  • [Presentation] Tumor-infiltrating CD11b+cells have function of myeloid derived suppressor cells2008

    • Author(s)
      Umemura, N., Saio, M., Nonaka, K., Suwa, T., Shibata, T., Takami, T.
    • Organizer
      The 10th Interbational Symposium on Dendritic cells
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2008-10-03
    • Related Report
      2008 Annual Research Report
  • [Presentation] IL-2 and soluble from TNF-receptor type II inhibits maturation of tumor-infiltrating mononuclear phagocytes in vivo2008

    • Author(s)
      Nonaka, K., Saio, M., Umemura, N., Takahashi, T., Osada, S., Yoshida, K., and Takami, T.
    • Organizer
      The 10th International Symposium on Dendritic cells
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2008-10-02
    • Related Report
      2008 Final Research Report
  • [Presentation] IL-2 and soluble from TNF-receptor type II inhibits maturation of tumor-in filtrating mononuclear phagocytes in vivo.2008

    • Author(s)
      Nonaka, K., Saio, M., Umemura, N., Takahashi, T., Osada, S., Yoshida, K., Takami, T.
    • Organizer
      The 10th Interbational Symposium on Dendritic cells
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2008-10-02
    • Related Report
      2008 Annual Research Report
  • [Presentation] 腫瘍内浸潤単核食細胞の成熟におけるヘルパーT細胞の役割の検討2008

    • Author(s)
      野中健一, 齊尾征直, 高橋孝夫, 山口和也, 長田真二, 川口順敬, 吉田和弘
    • Organizer
      第29回癌免疫外科研究会
    • Place of Presentation
      東京
    • Year and Date
      2008-06-20
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 骨髄球由来抑制細胞の分化に関与する腫瘍由来因子の検討2008

    • Author(s)
      鬼頭勇輔, 諏訪達彦, 白俊丞, 包麗紅, 齊尾征直, 高見剛
    • Organizer
      第97回日本病理学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2008-05-16
    • Related Report
      2008 Final Research Report
  • [Presentation] 腫瘍内浸潤骨髄球由来抑制細胞に対するサイトカイン療法の影響2008

    • Author(s)
      諏訪達彦, 齊尾征直, 鬼頭勇輔, 包麗紅, 白俊丞, 高見剛
    • Organizer
      第97回日本病理学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2008-05-16
    • Related Report
      2008 Final Research Report
  • [Presentation] 腫瘍内浸潤骨髄球由来抑制細胞の単球系分画と腫瘍随伴マクロファージの差異に関する検討2008

    • Author(s)
      齊尾征直, 諏訪達彦, 鬼頭勇輔, 白俊丞, 包麗紅, 高見剛
    • Organizer
      第97回日本病理学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2008-05-16
    • Related Report
      2008 Final Research Report
  • [Presentation] 骨髄球由来抑制細胞の分化に関与する腫瘍由来因子の検討2008

    • Author(s)
      鬼頭勇輔, 諏訪達彦, 白俊丞, 包麗紅, 齊尾征直, 高見剛
    • Organizer
      日本病理学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2008-05-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] 腫瘍内浸潤骨髄球由来抑制細胞に対するサイトカイン療法の影響2008

    • Author(s)
      諏訪達彦, 齊尾征直, 鬼頭勇輔, 包麗紅, 白俊丞, 高見剛
    • Organizer
      日本病理学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2008-05-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] 腫瘍内浸潤骨髄球由来抑制細胞の単球系分画と腫瘍随伴マクロファージの差異に関する検討2008

    • Author(s)
      齊尾征直, 諏訪達彦, 鬼頭勇輔, 白俊丞, 包麗紅, 高見剛
    • Organizer
      日本病理学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2008-05-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] Helper T cell affects the maturation of tumor-infiltrating myeloid derived suppressor cells in vivo2008

    • Author(s)
      Nonaka, K., Saio, M., Umemura, N., Frey, A., Ouyang, G., Suwa, T., Takahashi, T., Yoshida, K., and Takami, T.
    • Organizer
      AACR 99th Annual Meeting
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2008-04-13
    • Related Report
      2008 Final Research Report
  • [Presentation] Tumor-infiltrating immature myeloid cells do not mature into conventional or plasmacytoid dendritic cells but rather mature toward monocyte/macrophage at the tumor site2008

    • Author(s)
      Saio, M., Suwa, T., Nonaka, K., Umemura, N., Okada, M., Kito, Y., Bai, J., Ouyang, G., Bao, L., Hara, A., and Takami, T.
    • Organizer
      AACR 99th Annual Meeting
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2008-04-13
    • Related Report
      2008 Final Research Report
  • [Presentation] Tumor-infiltrating myeloid-derived suppressor cells are pleiotropic inflammed monocytes2008

    • Author(s)
      Umemura, N., Saio, M., Nonaka, K., Suwa, T., Shibata, T., and Takami, T.
    • Organizer
      AACR 99th Annual Meeting
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2008-04-13
    • Related Report
      2008 Final Research Report
  • [Presentation] Comparison of Tumor-infiltrating macrophages and Tumor-infiltrating dendritic cells in the central nervous system2007

    • Author(s)
      齊尾 征直
    • Organizer
      日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-03
    • Related Report
      2007 Annual Research Report
  • [Presentation] TNF expressed by tumor associated macrophages, but not microglia, can eliminate glioma2007

    • Author(s)
      齊尾 征直
    • Organizer
      米国癌学会
    • Place of Presentation
      ロサンゼルス
    • Year and Date
      2007-04-15
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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