Regulation of myeloid-derived suppressor cells in tumor microenvironment

• Project/Area Number: 22700894
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Tumor immunology
• Research Institution: Hokkaido University
• Principal Investigator: WAKITA Daiko 北海道大学, 遺伝子病制御研究所, 助教 (30555404)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 免疫抑制 / MDSCs / IL-6 / 腫瘍内微小環境 / マクロファージ / 好中球 / MDSC

Research Abstract

To develop effective cancer immunotherapy, we investigated the regulation mechanisms of myeloid-derived suppressor cells(MDSCs), a immunosuppressive cells in tumor-bearing host. We found that MDSCs obtained suppressive activity by exposing to tumor microenvironment. Blocking of IL-6 signaling by anti-IL-6 receptor monoclonal antibody eliminated MDSCs and inhibited tumor growth via anti-tumor T-cell responses.

Research Products

• [Journal Article] First clinical trial of cancer vaccine therapy with artificially synthesized helper/killer-hybrid epitope long peptide ofMAGE-A4 cancer antigen (2012)
  • Author(s): Takahashi N, Ohkuri T, Homma S, Ohtake J, Wakita D, Togashi Y, Kitamura H, Todo S, Nishimura T
  • Journal Title: Cancer Sci Volume: 103(1) Issue: 1 Pages: 150-3
  • DOI: 10.1111/j.1349-7006.2011.02106.x
  • Peer Reviewed
• [Journal Article] IFN-γ elevates airway hyper-responsiveness via up-regulation of neurokinin A/neurokinin-2 receptor signaling in a severe asthma model (2012)
  • Author(s): Kobayashi M, Ashino S, Shiohama Y, Wakita D, Kitamura H, Nishimura T
  • Journal Title: Eur J Immunol Volume: 42(2) Issue: 2 Pages: 393-402
  • DOI: 10.1002/eji.201141845
  • Peer Reviewed
• [Journal Article] 巷間で行われるリンパ球移入療法の問題点 (2012)
  • Author(s): 西村孝司、脇田大功、大栗敬幸、富樫裕二、北村秀光
  • Journal Title: メジカルビュー社 Volume: Vol.27, No.12 Pages: 124-133
• [Journal Article] IL-17/IFN-γdouble producing CD8+T(Tc17/IFN-γ) cells : A novel cytotoxic T-cell subset converted from Tc17 cells by IL-12 (2011)
  • Author(s): Tajima M, Wakita D, Satoh T, Kitamura H, Nishimura T.
  • Journal Title: Int Immunol Volume: 23(12) Pages: 751-9
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22039016(*equallycontributed)
  • Peer Reviewed
• [Journal Article] Phagocytosis of liposome particles by rat splenic immature monocytes makes them transiently and highly immunosuppressive (2011)
  • Author(s): Takahashi D, Azuma H, Sakai H, Sou K, Wakita D, Abe H, Fujihara N, Horinouchi H, Nishimura T, Kobayashi K, Ikeda H.
  • Journal Title: J Pharmacol Exp Ther Volume: 337(1) Pages: 42-9
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/21212161
  • Peer Reviewed
• [Journal Article] Blockade of IL-6-signaling inhibits the pathogenesis of CD4(+) T cell-mediated lethal graft-versus-host reaction against minor histocompatibility antigen (2011)
  • Author(s): Noguchi D, Wakita D, Ohkuri T, Tajima M, Chamoto K, Kitamura H, Nishimura T.
  • Journal Title: Immunol Lett Volume: 136(2) Pages: 146-55
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/21256159
  • Peer Reviewed
• [Journal Article] Toll-like receptor-dependent IL-12 production by dendritic cells is required for activation of natural killer cell-mediated Type-1 immunity induced by Chrysanthemum Coronarium L (2011)
  • Author(s): Tanaka S, Koizumi SI, Masuko K, Makiuchi N, Aoyagi Y, Quivy E, Mitamura R, Kano T, Ohkuri T, Wakita D, Chamoto K, Kitamura H, Nishimura T.
  • Journal Title: Int Immunopharmacol Volume: 11(2) Pages: 226-32
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/21144920
  • Peer Reviewed
• [Journal Article] The extract of Japanese soybean, Kurosengoku activates the production of IL-12 and IFN-γby DC or NK1. 1(+) cells in a TLR4-and TLR2-dependent manner (2011)
  • Author(s): Tanaka S, Koizumi S, Makiuchi N, Aoyagi Y, Quivy E, Mitamura R, Kano T, Wakita D, Chamoto K, Kitamura H, Nishimura T.
  • Journal Title: Cell Immunol Volume: 266(2) Pages: 135-42
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/20971456
  • Peer Reviewed
• [Journal Article] 腫瘍微小環境由来TGF-によって誘導される腫瘍増殖促進免疫制御細胞群の性状とその克服によるがん免疫治療 (2011)
  • Author(s): 西村孝司、脇田大功
  • Journal Title: 臨床免疫・アレルギー科 Volume: 56(1) Pages: 7-17
• [Journal Article] がん特異的な細胞治療の現状 (2011)
  • Author(s): 西村孝司、脇田大功、富樫裕二、北村秀光
  • Journal Title: カレントテラピー Volume: 29(12) Pages: 61-66
• [Journal Article] IL-17/IFN-γ double producing CD8+T (Tc17/IFN-γ) cells : A novel cytotoxic T-cell subset converted from Tc17 cells by IL-12 (2011)
  • Author(s): Masaki Tajima, et al
  • Journal Title: International Immunology Volume: 23 Issue: 12 Pages: 751-759
  • DOI: 10.1093/intimm/dxr086
  • Peer Reviewed
• [Journal Article] Phagocytosis of liposome particles by rat splenic immature monocytes makes them transiently and highly immunosuppressive in ex vivo culture conditions (2011)
  • Author(s): Takahashi D, Nishimura T, et al.
  • Journal Title: J Pharmacol Exp Ther. Volume: 337 Issue: 1 Pages: 42-49
  • DOI: 10.1124/jpet.110.172510
  • Peer Reviewed
• [Journal Article] 腫瘍微小環境由来TGF-bによって誘導される腫瘍増殖促進免疫制御細胞群の性状とその克服によるがん免疫治療 (2011)
  • Author(s): 西村孝司、脇田大功
  • Journal Title: 臨床免疫・アレルギー科 Volume: 56 Pages: 7-17
• [Journal Article] がん特異的な細胞治療の現状 (2011)
  • Author(s): 西村孝司、脇田大功, 他
  • Journal Title: カレントテラピー Volume: 29 Pages: 61-66
• [Journal Article] Toll-like receptor-dependent IL-12 production by dendritic cells is required for activation of natural killer cell-mediated Type-1 immunity in duced by Chrysanthemum Coronarium L. (2011)
  • Author(s): Sachi Tanaka, Daiko Wakita, et al.
  • Journal Title: International Immunopharmacology Volume: 11 Pages: 226-232
  • Peer Reviewed
• [Journal Article] Extract of Japanese soybean, Kurosengoku (Glycine max), activates Type-1 immunity via IL-12 production in a Toll-like receptor 2- and 4-dependent manner. (2011)
  • Author(s): Sachi Tanaka, Daiko Wakita, et al.
  • Journal Title: Cellular Immunology Volume: 11 Pages: 226-232
  • Peer Reviewed
• [Journal Article] Blockade of IL-6-signaling inhibits the pathogenesis of CD4(+) T cell-mediated lethal graft-versus-host reaction against minor histocompatibility antigen. (2011)
  • Author(s): Daisuke Noguchi, Daiko Wakita, et al.
  • Journal Title: Immunology Letters Volume: 136 Pages: 146-155
  • Peer Reviewed
• [Journal Article] 1α,25-Dihydroxyvitamin D3 and all-trans retinoic acid synergistically inhibit the differentiation and expansion of Th17 cells. (2011)
  • Author(s): Utako Ikeda, Daiko Wakita, et al
  • Journal Title: Cellular Immunology Volume: 266 Pages: 135-142
  • Peer Reviewed
• [Journal Article] 1α, 25-Dihydroxyvitamin D3 and all-trans retinoic acid synergistically inhibit the differentiation and expansion of Th17 cells (2010)
  • Author(s): Ikeda U, Wakita D, Ohkuri T, Chamoto K, Kitamura H, Iwakura Y, Nishimura T.
  • Journal Title: Immunol Lett Volume: 134(1) Pages: 7-16
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/20655952
  • Peer Reviewed
• [Journal Article] Tumor-infiltrating IL-17-producing gammadelta T cells support the progression of tumor via promoting angiogenesis (2010)
  • Author(s): Wakita D, Sumida K, Iwakura Y, Nishikawa H, Ohkuri T, Chamoto K, Kitamura H, Nishimura T.
  • Journal Title: Eur J Immunol Volume: 40(7) Pages: 1927-37
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/20397212
  • Peer Reviewed
• [Journal Article] 活性型ビタミンD_3とall-transレチノイン酸(ATRA)によるTh17細胞の分化制御とその疾病治療への応用 (2010)
  • Author(s): 池田詩子、但馬正樹、芦野滋、脇田大功、北村秀光, 西村孝司
  • Journal Title: 臨床免疫・アレルギー科 Volume: 53(3) Pages: 247-259
• [Journal Article] Tumor-infiltrating IL-17-producing gammadelta T cells support the progression of tumor via promoting angiogenesis. (2010)
  • Author(s): Daiko Wakita, et al.
  • Journal Title: Europian Journal of Immunology Volume: 40 Pages: 1927-1937
  • Peer Reviewed
• [Journal Article] 巷間で行われるリンパ球移入療法の問題点 (2010)
  • Author(s): 西村孝司、脇田大功, 他
  • Journal Title: 月刊Mebio Volume: 27 Pages: 124-133
• [Journal Article] Th17細胞による気道過敏反応増強とその機序Th1/Th細胞依存的気道炎症との異同 (2010)
  • Author(s): 西村孝司、脇田大功, 他
  • Journal Title: 臨床免疫・アレルギー科 Volume: 54 Pages: 631-638
• [Journal Article] Th17細胞による気道過敏反応増強とその機序Th1/Th細胞依存的気道炎症との異同
  • Author(s): 西村孝司、脇田大功、小林稔、北村秀光、芦野滋
  • Journal Title: 臨床免疫・アレルギー科 Volume: 54(6) Pages: 631-638
• [Presentation] IL-17産生γδT細胞による慢性炎症の遺伝子支配と発がんへの関与/Genetic control of chronic inflammation mediated by IL-17-producingγδT cells during carcinogenesis (2011)
  • Author(s): 脇田大功、角田健太郎、佐藤崇之、寺田聖、岩倉洋一郎、西川博嘉、北村秀光、西村孝司
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2011-11-27
• [Presentation] Genetic control of chronic inflammation mediated by IL-17-producing γδT cells during carcinogenesis (2011)
  • Author(s): 脇田大功, 他
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2011-11-27
• [Presentation] Cancer-associated inflammation mediated by IL-17-producing T cells and its genetic control(IL-17産生γδT細胞を介した炎症性発がん機構とその遺伝子支配) (2011)
  • Author(s): 脇田大功、角田健太郎、佐藤崇之、寺田聖、西川博嘉、岩倉洋一郎、北村秀光、西村孝司
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-03
• [Presentation] Caneer-associated inflammation mediated by IL-17-producing γδT cells and its genetic control (2011)
  • Author(s): 脇田大功, 他
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知)
  • Year and Date: 2011-10-03
• [Presentation] 慢性炎症微小環境におけるIL-17産生γδT細胞制御機構とその発がんへの関与 (2011)
  • Author(s): 脇田大功、角田健太郎、佐藤崇之、寺田聖、西川博嘉、岩倉洋一郎、北村秀光、西村孝司
  • Organizer: 第15回日本がん免疫学会総会
  • Place of Presentation: 千里ライフサイエンスセンター
  • Year and Date: 2011-07-01
• [Presentation] 慢性炎症微小環境におけるIL-17産生γδT細胞制御機構とその発がんへの関与 (2011)
  • Author(s): 脇田大功, 他
  • Organizer: 第15回日本がん免疫学会総会
  • Place of Presentation: 千里ライフサイエンスセンター(大阪)
  • Year and Date: 2011-07-01
• [Presentation] IL-17産生T細胞による発癌促進機構 (2011)
  • Author(s): 脇田大功
  • Organizer: 第7回北海道癌免疫制御研究会
  • Place of Presentation: 札幌パークホテル
  • Year and Date: 2011-06-11
• [Presentation] IL-17産生γδT細胞による発癌促進機構 (2011)
  • Author(s): 脇田大功
  • Organizer: 第7回北海道癌免疫制御研究会
  • Place of Presentation: 札幌パークホテル(北海道)(招待講演)
  • Year and Date: 2011-06-11
• [Presentation] IL-17-producingγδT cells induce genetically controlled chronic inflammation and promote carcinoma development in BALB/c mouse skin (2011)
  • Author(s): Daiko Wakita, Kentaro Sumida, Takayuki Satoh, Yoichiro Iwakura, Hiroyoshi Nishikawa, Hidemitsu Kitamura, Takashi Nishimura.
  • Organizer: The Joint International Meeting of The 76th Annual Meeting of the Japanese Society for Interferon and Cytokine Research, The 19th International Symposium of Macrophage Molecular and Cell Bilogy2011
  • Place of Presentation: 全日空ゲートタワーホテル大阪
  • Year and Date: 2011-05-25
• [Presentation] IL-17-producing γδT cells induce genetically controlled chronic inflammation and promote carcinoma development in BALB/c mouse skin (2011)
  • Author(s): 脇田大功, 他
  • Organizer: The Joint International Meeting of The 76th Annual Meeting of the Japanese Society for Interferon and Cytokine Research
  • Place of Presentation: 全日空ゲートタワーホテル大阪(大阪)
  • Year and Date: 2011-05-25
• [Presentation] Genetic control of generation of IL-17-rpducing cells during carcinogenesis.(発癌過程におけるIL-17産生細胞制御の遺伝支配) (2010)
  • Author(s): 脇田大功、角田健太郎、佐藤崇之、久保田那月、西川博嘉、岩倉洋一郎、大栗敬幸、北村秀光、西村孝司
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: リーガロイヤルホテル大阪/大阪国際会議場
  • Year and Date: 2010-09-22
• [Presentation] Genetic control of generation of IL-17-rpducing cells during carcinogenesis.(発癌過程におけるIL-17産生細胞制御の遺伝支配) (2010)
  • Author(s): 脇田大功, 他
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: リーガロイヤルホテル大阪/大阪国際会議場(大阪府)
  • Year and Date: 2010-09-22
• [Presentation] A crucial role for IL-17-producingγδT cells as a major tumor-promoting T cells at tumor microenvironments (2010)
  • Author(s): D. Wakita, T. Nishimura
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-08-27
• [Presentation] A crucial role for IL-17-producing γδ T cells as a major tumor-promoting T cells at tumor microenvironments (2010)
  • Author(s): Daiko Wakita, et al.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2010-08-27
• [Presentation] 発癌過程ほよび腫瘍増殖におけるIL-17産生細胞の意義とその遺伝子支配 (2010)
  • Author(s): 脇田大功、角田健太郎、佐藤崇之、久保田那月、西川博嘉、岩倉洋一郎、大栗敬幸、北村秀光、西村孝司
  • Organizer: 第14回がん免疫学会総会
  • Place of Presentation: KKRホテル熊本
  • Year and Date: 2010-07-23
• [Presentation] 発癌過程ほよび腫瘍増殖におけるIL-17産生細胞の意義とその遺伝子支配 (2010)
  • Author(s): 脇田大功, 他
  • Organizer: 第14回がん免疫学会総会
  • Place of Presentation: KKRホテル熊本(熊本県)
  • Year and Date: 2010-07-23
• [Presentation] IL-6依存的に異常増殖する担癌マウスimmature myeloid cellsの制御と癌治療への応用 (2010)
  • Author(s): 脇田大功、角田健太郎、北村秀光、西村孝司
  • Organizer: 第75回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 北九州国際会議場
  • Year and Date: 2010-06-25
• [Presentation] IL-6依存的に異常増殖する担癌マウスimmature myeloid cellsの制御と癌治療への応用 (2010)
  • Author(s): 脇田大功, 他
  • Organizer: 第75回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 北九州国際会議場(福岡県)
  • Year and Date: 2010-06-25
• [Book] ヘルパーT細胞を軸とした抗腫瘍免疫の制御:基盤研究から臨床応用まで」.シーエムシー出版がん免疫療法.実用化へのチャレンジ (2010)
  • Author(s): 西村孝司、脇田大功、大栗敬幸、北村秀光
• [Remarks]
  • URL: http://www.igm.hokudai.ac.jp/immreg/