Functional conversion of tumor-supporting myeloid cells to tumoricidal effectors by dsRNA adjuvant

• Project/Area Number: 22790371
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Hokkaido University
• Principal Investigator: SHIME Hiroaki 北海道大学, 大学院・医学研究科, 助教 (70372133)
• 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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 癌 / アジュバント / TLR3 / マクロファージ / 癌免疫療法 / 2本鎖RNA / TICAM-1 / TRIF / 抗腫瘍免疫 / 自然免疫 / TLR / 腫瘍免疫 / 免疫抑制 / MDSC / poly I:C / 二本鎖RNA

Research Abstract

In many cancer patients, immune system is subverted by immunosuppressive cells as well as tumor-derived factors, which contributes to tumor progression. Tumor-associated macrophages with immunosuppressive, M2-like phenotype support the tumor growth by several mechanisms. Here, we show that double-stranded RNA(dsRNA) adjuvant induces growth retardation of 3LL tumor by converting tumor-supporting macrophages to tumoricidal effectors through the activation of TLR3-TICAM-1 signaling pathway

Research Products

• [Journal Article] TAMable tumor-associated macrophages in response to innate RNA sensing (2012)
  • Author(s): Seya T, Shime H, Matsumoto M
  • Volume: (in press)
  • NAID: 120005228653
  • Peer Reviewed
• [Journal Article] Toll-like receptor 3 signaling converts tumor-supporting myeloid cells to tumoricidal effectors (2012)
  • Author(s): Shime H, Matsumoto M, Oshiumi H, Tanaka S, Nakane A, Iwakura Y, Tahara H, Inoue N, Seya T
  • Journal Title: Proc Natl Acad Sci USA Volume: 109(6) Pages: 2066-71
  • Peer Reviewed
• [Journal Article] Toll-like receptor 3 signaling converts tumor-supporting myeloid cells to tumoricidal effectors (2012)
  • Author(s): H.Shime
  • Journal Title: Proc Natl Acad Sci USA Volume: 109 Issue: 6 Pages: 2066-2071
  • DOI: 10.1073/pnas.1113099109
  • Peer Reviewed
• [Journal Article] A rapid and simple PCR method for identifying isolates of the genus Azospirillum within populations of rhizosphere bacteria (2011)
  • Author(s): Shime-Hattori A, Kobayashi S, Ikeda S, Asano R, Shime H, Shinano T
  • Journal Title: J Appl Microbiol Volume: 111(4) Pages: 915-924
  • Peer Reviewed
• [Journal Article] Development of mouse hepatocyte lines permissive for hepatitis C virus (HCV) (2011)
  • Author(s): Aly, H.H., H.Oshiumi, H.Shime, M.Matsumoto, T.Wakita, K.Shimotohno, T.Seya
  • Journal Title: Plos ONE Volume: 6 Issue: 6 Pages: e21284-e21284
  • DOI: 10.1371/journal.pone.0021284
  • NAID: 120003169041
  • Peer Reviewed
• [Journal Article] Development of monoclonal antibodies that specifically interact with necrotic lymphoma cells (2011)
  • Author(s): Wakasa K, Shime H, Kurita-Taniguchi M, Matsumoto M, Imamura M, Seya T
  • Journal Title: Microbiol Immunol Volume: 55(5) Pages: 373-7
  • NAID: 10031121481
  • Peer Reviewed
• [Journal Article] Raftlin Is Involved in the Nucleocapture Complex to Induce Poly(I : C)-mediated TLR3 Activation (2011)
  • Author(s): Watanabe A, Tatematsu M, Saeki K, Shibata S, Shime H, Yoshimura A, Obuse C, Seya T, Matsumoto M
  • Journal Title: J Biol Chem Volume: 286(12) Pages: 10702-11
  • Peer Reviewed
• [Journal Article] 自然免疫と癌治療 (2011)
  • Author(s): 瀬谷司、押海裕之、志馬寛明、松本美佐子
  • Journal Title: 実験医学 Volume: vol.29 Pages: 111-118
• [Journal Article] 腫瘍浸潤myeloid cellsによる免疫抑制 (2011)
  • Author(s): 志馬寛明、松本美佐子、瀬谷司
  • Journal Title: 臨床免疫・アレルギー科 Volume: vol.56 Pages: 23-30
• [Journal Article] Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2 (2011)
  • Author(s): Sawahata R, Shime H, Yamazaki S, Inoue N, Akazawa T, Fujimoto Y, Fukase K, Matsumoto M, Seya T
  • Journal Title: Microbes Infect Volume: 13(4) Pages: 350-8
  • NAID: 120002912001
  • Peer Reviewed
• [Journal Article] IL-23-dependent and-independent enhancement pathways of IL-17A production by lactic acid (2011)
  • Author(s): Yabu M, Shime H, Hara H, Saito T, Matsumoto M, Seya T, Akazawa T, Inoue N
  • Journal Title: Int. Immunol Volume: 23 Pages: 29-41
  • Peer Reviewed
• [Journal Article] Natural killer cell activation secondary to innate pattern sensing (2011)
  • Author(s): Seya T, Kasamatsu J, Azuma M, Shime H, Matsumoto M
  • Journal Title: J Innate Immun Volume: 3(3) Pages: 264-73
  • Peer Reviewed
• [Journal Article] Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2 (2011)
  • Author(s): Sawahata, R., Shime, H., Yamazaki, S., Inoue, N., Akazawa, T., Fujimoto, Y., Fukase, K., Matsumoto, M. and Seya, T.
  • Journal Title: Microbes and Infection Volume: 13 Issue: 4 Pages: 350-358
  • DOI: 10.1016/j.micinf.2010.12.003
  • NAID: 120002912001
  • Peer Reviewed
• [Journal Article] Development of monoclonal antibodies that specifically interact with necrotic lymphoma cells (2011)
  • Author(s): Wakasa K, Shime H (equally contributed)
  • Journal Title: Microbiol Immunol Volume: 55 Issue: 5 Pages: 373-377
  • DOI: 10.1111/j.1348-0421.2011.00319.x
  • NAID: 10031121481
  • Peer Reviewed
• [Journal Article] 腫瘍浸潤myeloid cellsによる免疫抑制 (2011)
  • Author(s): 志馬寛明
  • Journal Title: 臨床免疫・アレルギー科 Volume: 56 Pages: 23-30
• [Journal Article] IL-23-dependent and -independent enhancement pathways of IL-17A production by lactic acid. (2011)
  • Author(s): Yabu M, Shime H
  • Journal Title: International Immunology Volume: 23 Pages: 29-41
  • Peer Reviewed
• [Journal Article] Raftlin is involved in the nucleocapture complex to induce poly(I:C)-mediated TLR3 activation. (2011)
  • Author(s): Watanabe A
  • Journal Title: The Journal of Biological chemistry Volume: 286 Pages: 10702-10711
  • Peer Reviewed
• [Journal Article] 自然免疫と癌治療 (2011)
  • Author(s): 瀬谷司
  • Journal Title: 実験医学増刊 Volume: 29 Pages: 111-118
• [Journal Article] Pattern recognition receptors of innate immunity and their application to tumor immunotherapy (2010)
  • Author(s): Seya T, Shime H, Ebihara T, Oshiumi H, Matsumoto M
  • Journal Title: Cancer Sci Volume: 101 Pages: 313-320
  • NAID: 10026587432
  • Peer Reviewed
• [Journal Article] Adjuvant engineering for cancer immunotherapy : development of a synthetic TLR2 ligand with increased cell adhesion (2010)
  • Author(s): Akazawa T, Inoue N, Shime H, Kodama K, Matsumoto M, Seya T
  • Journal Title: Cancer Sci Volume: 101 Pages: 1596-1603
  • NAID: 10026594411
  • Peer Reviewed
• [Journal Article] Adjuvant engineering for cancer immunotherapy : Development of a synthetic TLR2 ligand with increased cell adhesion. (2010)
  • Author(s): Akazawa T
  • Journal Title: Cancer Science Volume: 101 Pages: 1596-1603
  • Peer Reviewed
• [Journal Article] Pattern recognition receptors of innate immunity and their application to tumor immunotherapy. (2010)
  • Author(s): Seya T
  • Journal Title: Cancer Science Volume: 101 Pages: 313-320
  • Peer Reviewed
• [Presentation] Tumoricidal activity of tumor-associated macrophages induced by RNA adjuvant therapy (2011)
  • Author(s): Shime H
  • Organizer: 日本免疫学会
  • Place of Presentation: 幕張メッセ(千葉県)
  • Year and Date: 2011-12-28
• [Presentation] Establishment of HCV replication in mouse hepatocytes through the modulation of mouse innate immune response (2011)
  • Author(s): Aly HH
  • Organizer: 日本免疫学会
  • Place of Presentation: 幕張メッセ(千葉県)
  • Year and Date: 2011-12-27
• [Presentation] 癌で増加するCD11bGr1陽性細胞は、二本鎖RNAアジュバントの刺激により (2011)
  • Author(s): 児島絢子
  • Organizer: NK細胞活性化能を獲得する日本分子生物学会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-12-14
• [Presentation] Tumor-infiltrating macrophages turn tumoricidal through TLR3/TICAM-1 signal by dsRNA stimulation (2011)
  • Author(s): Shime H
  • Organizer: The 16th Korea-Japan cancer research workshop
  • Place of Presentation: 北海道大学(札幌市)
  • Year and Date: 2011-12-10
• [Presentation] Tumoricidal activity of tumor-associated macrophages activated by RNA adjuvant (2011)
  • Author(s): Shime H
  • Organizer: 日本癌学会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-04
• [Presentation] 二本鎖RNAアジュバントによる腫瘍随伴マクロファージの活性化と抗腫瘍免疫応答 (2011)
  • Author(s): 志馬寛明
  • Organizer: 日本がん免疫学会
  • Place of Presentation: 千里ライフサイエンスセンタービル(大阪府)
  • Year and Date: 2011-06-30
• [Presentation] RNA adjuvant : multi-directional induction of antitumor effectors by dendritic cells (2010)
  • Author(s): Seya T
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-09-23
• [Presentation] Tumor-infiltrating myeloid cells evoke in vivo tumoricidal activity by RNA adjuvant therapy (2010)
  • Author(s): Shime H
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-09-22
• [Presentation] Tumor-infiltrating myeloid cells evoke in vivo tumoricidal activity by RNA adjuvant therapy (2010)
  • Author(s): 志馬寛明
  • Organizer: 第69回 日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-09-22
• [Presentation] Possible contribution of tumor-infiltrating myeloid cells to anti-tumor immune response during RNA adjuvant therapy (2010)
  • Author(s): 志馬寛明
  • Organizer: 平成22年度がん若手研究者ワークショップ
  • Place of Presentation: アートランドホテル蓼科(長野)
  • Year and Date: 2010-09-03
• [Presentation] Possible contribution of tumor-infiltrating myeloid cells to anti-tumor immune response during RNA adjuvant therapy (2010)
  • Author(s): 志馬寛明
  • Organizer: 平成22年度 がん若手研究者ワークショップ
  • Place of Presentation: アートランドホテル蓼科(長野)
  • Year and Date: 2010-09-03
• [Presentation] 樹状細胞と腫瘍浸潤マクロファージのアジュバント応答 (2010)
  • Author(s): 志馬寛明
  • Organizer: 第14回日本がん免疫学会総会
  • Place of Presentation: KKRホテル熊本(熊本)
  • Year and Date: 2010-07-23
• [Presentation] 樹状細胞と腫瘍浸潤マクロファージのアジュバント応答 (2010)
  • Author(s): 志馬寛明
  • Organizer: 第14回 日本がん免疫学会総会
  • Place of Presentation: KKRホテル熊本(熊本)(招待講演)
  • Year and Date: 2010-07-23
• [Book] Advanced technologies for adjuvant research and development抗がん免疫アジュバントの開発と現状 (2011)
  • Author(s): 瀬谷司,佐藤治子,志馬寛明,松本美佐子
  • Publisher: CMC出版
• [Remarks] 新聞報道等
  • URL: http://www.hucc.hokudai.ac.jp/~e20536/
• [Remarks] 北大広報(2012. 1)
• [Remarks] マイナビニュース(2012. 1)
• [Remarks] 北海道医療新聞(2012. 1)
• [Remarks] 日刊工業新聞(2012. 1)
• [Remarks] Newton Doctor(2012. 3)
• [Remarks] 科学新聞(2012. 2)
• [Remarks]
  • URL: http://www.hucc.hokudai.ac.jp/~e20536/
• [Remarks]
  • URL: http://www.hucc.hokudai.ac.jp/~e20536/