Study of the molecular bases for the dynamics and dysfunction of dendritic cell subsets in tumor-bearing host

• Project/Area Number: 21790379
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: The University of Tokyo
• Principal Investigator: UEHA Satoshi The University of Tokyo, 大学院・医学系研究科, 助教 (00447385)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 腫瘍 / 樹状細胞 / 癌 / ケモカイン / 免疫学

Research Abstract

We examined the tumor-infiltrating DC subsets with the potential to migrate to draining-lymph nodes and identified CCR7^+ MHC class II^<hi> TIDCs as the precursor of lymph node migratory DCs with antigen uptake and presentation potential. Chemokine receptor KO (CKO) mice and the wild type vs CKO mixed bone marrow chimera mice revealed that CCR2 partially mediates the accumulation of the TIDCs. We also found that the TIDCs were relatively resistant to the anti-cancer drug in vivo. Based on these results, we expect that the combination therapy of anti-cancer drug and CCR2 targeted drug that augment TIDCs would provide a novel anti-cancer immunotherapy.

Research Products

• [Journal Article] Myeloid cell population dynamics in healthy and tumor-bearing mice. (2011)
  • Author(s): Ueha S, Shand FH, Matsushima K.
  • Journal Title: Int Immunopharmacol. 掲載確定(印刷中)
  • Peer Reviewed
• [Journal Article] Myeloid cell population dynamics in healthy and tumor-bearing mice (2011)
  • Author(s): Ueha S, et al.
  • Journal Title: Int Immunopharmacol Volume: (掲載確定 in press)
  • Peer Reviewed
• [Journal Article] Involvement of CD11b(+) GR-1 (low) cells in autoimmune disorder in MRL-Fas (lpr) mouse. (2010)
  • Author(s): Iwata Y, Furuichi K, Kitagawa K, Hara A, Okumura T, Kokubo S, Shimizu K, Sakai N, Sagara A, Kurokawa Y, Ueha S, Matsushima K, Kaneko S, Wada T.
  • Journal Title: Clin Exp Nephrol. 14 Pages: 411-417
  • Peer Reviewed
• [Journal Article] Deficiency of chemokine receptor CCR1 causes osteopenia due to impaired functions of osteoclasts and osteoblasts. (2010)
  • Author(s): Hoshino A, Iimura T, Ueha S, Hanada S, Maruoka Y, Mayahara M, Suzuki K, Imai T, Ito M, Manome Y, Yasuhara M, Kirino T, Yamaguchi A, Matsushima K, Yamamoto K.
  • Journal Title: J Biol Chem. 285 Pages: 28826-28837
  • Peer Reviewed
• [Journal Article] Bone marrow graft-versus-host disease : early destruction of hematopoietic niche following MHC-mismatched hematopoietic stem cell transplantation. (2010)
  • Author(s): Shono Y, Ueha S, Wang Y, Abe J, Kurachi M, Matsuno Y, Sugiyama T, Nagasawa T, Imamura M, Matsushima K.
  • Journal Title: Blood. 115 Pages: 5401-5411
  • Peer Reviewed
• [Journal Article] Efficient cross-presentation of soluble exogenous antigens introduced into dendritic cells using a weak-based amphiphilic peptide. (2010)
  • Author(s): Ikeuchi N, Futami J, Hosoi A, Noji S, Kurachi M, Ueha S, Fujii S, Yamada H, Matsushima K, Moriyasu F, Kakimi K.
  • Journal Title: Biochem Biophys Res Commun. 392 Pages: 217-222
  • Peer Reviewed
• [Journal Article] Involvement of CD11b+ GR-1 low cells in autoimmune disorder in MRL-Fas lpr mouse (2010)
  • Author(s): Iwata Y, et al.
  • Journal Title: Clin Exp Nephrol Volume: 14 Pages: 411-417
  • Peer Reviewed
• [Journal Article] Deficiency of chemokine receptor CCR1 causes osteopenia due to impaired functions of osteoclasts and osteoblasts (2010)
  • Author(s): Hoshino A, et al.
  • Journal Title: J Biol Chem. Volume: 285 Pages: 28826-28837
  • Peer Reviewed
• [Journal Article] Bone marrow graft-versus-host disease : early destruction of hematopoietic niche after MHC-mismatched hematopoietic stem cell transplantation (2010)
  • Author(s): Shono Y, et al.
  • Journal Title: Blood Volume: 115 Pages: 5401-5411
  • Peer Reviewed
• [Journal Article] Efficient cross-presentation of soluble exogenous antigens introduced into dendritic cells using a weak-based amphiphilic peptide (2010)
  • Author(s): Ikeuchi N, et al.
  • Journal Title: Biochem Biophys Res Commun 392 Pages: 217-222
  • Peer Reviewed
• [Presentation] 骨髄GVHD:同種造血幹細胞移植に伴う骨髄造血ニッチの破壊 (2011)
  • Author(s): 上羽悟史
  • Organizer: The 7^<th> Osteoimmunology Forum
  • Place of Presentation: Tokyo, Japan (Tokyo University)
  • Year and Date: 2011-02-02
• [Presentation] Depletion of allo-CD4 T cells protects hematopoietic niche while preserves graft-versus-tumor effects after allo-HSCT. (2010)
  • Author(s): UEHA Satoshi, et al.
  • Organizer: The 69^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Osaka International Convention center (Osaka)
  • Year and Date: 2010-09-22
• [Presentation] Depletion of allo-CD4 T cells protects hematopoietic niche while preserves graft-versus-tumor effects after allo-HSCT (2010)
  • Author(s): UEHA Satoshi, et al.
  • Organizer: The 69th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Osaka, Japan (Osaka International Convention Center)
  • Year and Date: 2010-09-22
• [Presentation] Dynamics of CCR7+ tumor-infiltrating dendritic cells that regulate anti-tumor immune responses. (2010)
  • Author(s): UEHA Satoshi, et al.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe Convention center (Kobe)
  • Year and Date: 2010-08-26
• [Presentation] Dynamics of CCR7+ tumor-infiltrating dendritic cells that regulate anti-tumor immune responses (2010)
  • Author(s): UEHA Satoshi, et al.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan (Kobe Convention Center)
  • Year and Date: 2010-08-26
• [Presentation] 抗腫瘍T細胞応答を制御するCCR7陽性腫瘍浸潤樹状細胞の動態 (2010)
  • Author(s): 上羽悟史, 他
  • Organizer: 第31回日本炎症・再生医学会
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2010-08-05
• [Presentation] 抗腫瘍T細胞応答を制御するCCR7陽性腫瘍浸潤樹状細胞の動態 (2010)
  • Author(s): 上羽悟史, 他
  • Organizer: 第31回日本炎症・再生医学会
  • Place of Presentation: 東京(京王プラザホテル)
  • Year and Date: 2010-08-05
• [Presentation] Depletion of allo-CD4 T cells protects hematopoietic niche while preserves graft-versus-tumor effects after allo-HSCT. (2010)
  • Author(s): UEHA Satoshi, et al.
  • Organizer: 14^<th> Annual Meeting of Japanese Association of Cancer Immunology.
  • Place of Presentation: KKR hotel Kumamoto (Kumamoto)
  • Year and Date: 2010-07-22
• [Presentation] Depletion of allo-CD4 T cells protects hematopoietic niche while preserves graft-versus-tumor effects after allo-HSCT (2010)
  • Author(s): UEHA Satoshi, et al.
  • Organizer: 14^<th> Annual Meeting of Japanese Association of Cancer Immunology.
  • Place of Presentation: Kumamoto, Japan (KKR Hotel Kumamoto)
  • Year and Date: 2010-07-22
• [Presentation] 抗腫瘍T細胞応答を制御するCCR7陽性腫瘍浸潤樹状細胞の動態 (2010)
  • Author(s): 上羽悟史, 他
  • Organizer: 第19回日本癌病態治療研究会
  • Place of Presentation: 都市センターホテル(東京)
  • Year and Date: 2010-06-30
• [Presentation] 抗腫瘍T細胞応答を制御するCCR7陽性腫瘍浸潤樹状細胞の動態 (2010)
  • Author(s): 上羽悟史, 他
  • Organizer: 第19回日本癌病態治療研究会
  • Place of Presentation: 東京(都市センターホテル)
  • Year and Date: 2010-06-30
• [Presentation] Destruction of Bone Marrow Osteoblastic Niche for Hematopoiesis Mediated by Donor CD4 T Cells after Allogeneic Hematopoietic Stem Cell Transplantation. (2010)
  • Author(s): UEHA Satoshi, et al.
  • Organizer: 3^<rd> International Conference on Osteoimmunology
  • Place of Presentation: Santorini (Greece)
  • Year and Date: 2010-06-20
• [Presentation] Destruction of Bone Marrow Osteoblastic Niche for Hematopoiesis Mediated by Donor CD4 T Cells after Allogeneic Hematopoietic Stem Cell Transplantation. (2010)
  • Author(s): UEHA Satoshi, et al.
  • Organizer: 3^<rd> International Conference on Osteoimmunology
  • Place of Presentation: Santorini, Greece.
  • Year and Date: 2010-06-20
• [Presentation] Dynamics of CCR7+ tumor-infiltrating dendritic cells that regulate anti-tumor immune responses. (2010)
  • Author(s): UEHA Satoshi, et al.
  • Organizer: 18^<th> International Symposium on Molecular Cell Biology of Macrophages
  • Place of Presentation: Parea Kumamoto (Kumamoto)
  • Year and Date: 2010-05-21
• [Presentation] DynamicsofCCR7+tumor-infiltratingdendriticcellsthatregulate anti-tumor immune responses (2010)
  • Author(s): UEHA Satoshi, et al.
  • Organizer: 18th International Symposium on Molecular Cell Biology of Macrophages 2010
  • Place of Presentation: Kumamoto, Japan (Parea Kumamoto)
  • Year and Date: 2010-05-21
• [Presentation] Identification of CCR7+MHC class IIhi dendritic cells in mouse tumor. (2010)
  • Author(s): Satoshi Ueha, et al.
  • Organizer: Keystone symposia
  • Place of Presentation: Keystone Resort (USA)
  • Year and Date: 2010-02-10
• [Presentation] Identification of CCR7^+MHC class II^<hi> dendritic cells in mouse tumor (2010)
  • Author(s): 上羽悟史
  • Organizer: Keystone symposia
  • Place of Presentation: Keystone Resort(USA)
  • Year and Date: 2010-02-10
• [Presentation] 骨髄GVHD:同種造血幹細胞移植に伴う骨髄造血ニッチの破壊 (2010)
  • Author(s): 上羽悟史
  • Organizer: The 7^<th> Osteoimmunology Forum
  • Place of Presentation: Tokyo University (Tokyo)
  • Year and Date: 2010-02-02
• [Presentation] Dynamic regulation of tumor-infiltrating myeloid-cells by chemokines. (2009)
  • Author(s): Satoshi Ueha, et al.
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2009-12-02
• [Presentation] Dynamic regulation of tumor-infiltrating myeloid-cells by chemokines (2009)
  • Author(s): 上羽悟史
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2009-12-02
• [Presentation] Identification of CCR7+MHC class IIhi dendritic cells in mouse tumor. (2009)
  • Author(s): Satoshi Ueha, et al.
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2009-09-25
• [Presentation] Identification of CCR7^+MHC class II^<hi> dendritic cells in mouse tumor (2009)
  • Author(s): 上羽悟史
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2009-09-25
• [Presentation] CHEMOKINE- MEDIATED RAPID TURNOVER OF INFLAMMATION-ASSOCIATED MACROPHAGES AND NEUTROPHILS IN TUMOR-BEARING MICE. (2009)
  • Author(s): Satoshi Ueha
  • Organizer: The 9^<th> World Congress on Inflammation
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2009-07-08
• [Presentation] CHEMOKINE-MEDIATED RAPID TURNOVER OF INFLAMMATION-ASSOCIATED MACROPHAGES AND NEUTROPHILS IN TUMOR-BEARING MICE (2009)
  • Author(s): 上羽悟史
  • Organizer: The 9th World Congress on Inflammation
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2009-07-08
• [Presentation] Identification of CCR7+MHC class IIhi dendritic cells in mouse tumor. (2009)
  • Author(s): Satoshi Ueha, et al.
  • Organizer: 第17回マクロファージ分子細胞生物学国際シンポジウム
  • Place of Presentation: 金沢KKRホテル(石川)
  • Year and Date: 2009-07-03
• [Presentation] Identification of CCR7^+MHC class II^<hi> dendritic cells in mouse tumor (2009)
  • Author(s): 上羽悟史
  • Organizer: 第17回マクロファージ分子細胞生物学国際シンポジウム
  • Place of Presentation: 金沢KKRホテル(石川)
  • Year and Date: 2009-07-03
• [Presentation] Identification of CCR7+MHC class IIhi dendritic cells in mouse tumor. (2009)
  • Author(s): Satoshi Ueha, et al.
  • Organizer: 第13回日本がん免疫学会総会
  • Place of Presentation: 北九州国際会議場(福岡)
  • Year and Date: 2009-06-25
• [Presentation] Identification of CCR7^+MHC class II^<hi> dendritic cells in mouse tumor (2009)
  • Author(s): 上羽悟史
  • Organizer: 第13回日本がん免疫学会総会
  • Place of Presentation: 北九州国際会議場(福岡)
  • Year and Date: 2009-06-25
• [Presentation] マウス皮下腫瘍モデルにおけるCCR7+腫瘍浸潤樹状細胞の同定 (2009)
  • Author(s): 上羽悟史, 他
  • Organizer: 第18回日本癌病態治療研究会
  • Place of Presentation: コラッセふくしま(福島)
  • Year and Date: 2009-06-19
• [Presentation] マウス皮下腫瘍モデルにおけるCCR7^+腫瘍浸潤樹状細胞の同定 (2009)
  • Author(s): 上羽悟史
  • Organizer: 第18回日本癌病態治療研究会
  • Place of Presentation: コラッセふくしま(福島)
  • Year and Date: 2009-06-19
• [Book] 臨床粘膜免疫 (2010)
  • Author(s): 清野宏 編
  • Publisher: シナジー
• [Book] 分子予防環境医学 (2010)
  • Author(s): 松島綱治 編
  • Publisher: 本の泉社
• [Book] 臨床粘膜免疫 (2010)
  • Author(s): 清野宏編
  • Total Pages: 736
  • Publisher: シナジー
• [Book] 分子予防環境医学 (2010)
  • Author(s): 松島綱治編
  • Total Pages: 850
  • Publisher: 本の泉社
• [Remarks] ホームページ
  • URL: http://www.prevent.m.u-tokyo.ac.jp/