Analysis of tumor-rejecting biological reactions induced by tumor specific immune responses

• Project/Area Number: 23300355
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor immunology
• Research Institution: Juntendo University
• Principal Investigator: TAKEDA Kazuyoshi 順天堂大学, 医学部, 准教授 (80272821)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥22,100,000 (Direct Cost: ¥17,000,000、Indirect Cost: ¥5,100,000); Fiscal Year 2013: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000); Fiscal Year 2012: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000); Fiscal Year 2011: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: 免疫監視 / 腫瘍免疫 / 癌治療 / 免疫エスケープ / NK細胞 / 腫瘍特異的 CTL / 免疫 / 抗体療法 / TRAIL / DR5 / 癌抗原 / 癌ワクチン療法 / CTL / IFN-γ / 肺転移 / 血管閉塞 / 細胞傷害活性

Research Abstract

This study was aiming to reveal the immune responses induced in tumor mass and tumor-rejecting biological responses induced by specific anti-tumor immune responses. I have reported that (1) Critical roles of IFN-gamma produced by primarily infiltrating NK cells for entire anti-tumor immune responses (2) Immune suppression by MHC Class II-dressed NK cells (3) novel therapy basing on the specific phenotypic changes of tumor infiltrating CTLs. I am now going to prepare the reports concerning the mechanisms that immune responses induce resistance against anti-tumor immune responses in targeted-tumor cells and the biological responses specifically induced in the rejected tumor mass.

Research Products

• [Journal Article] Phase I clinical study of multiple epitope peptide vaccine combined with chemoradiation therapy in esophageal cancer patients (2014)
  • Author(s): Iinuma H, Fukushima R, Inaba T,他全15名
  • Journal Title: J. Transl. Med Volume: 12(1) Issue: 1 Pages: 84-84
  • DOI: 10.1186/1479-5876-12-84
  • Peer Reviewed
• [Journal Article] A phase I study of combination vaccine treatment of five therapeutic epitope-peptides for metastatic colorectal cancer; safety, immunological response, and clinical outcome (2014)
  • Author(s): Hazama S, Nakamura Y, Takeuchi H, 他全13名
  • Journal Title: J. Transl. Med Volume: 12 (1) Issue: 1 Pages: 63-63
  • DOI: 10.1186/1479-5876-12-63
  • Peer Reviewed
• [Journal Article] Phase I clinical trial of multiple-peptide vaccination for patients with advanced biliary tract cancer (2014)
  • Author(s): Aruga A, Takeshita N, Kotera Y, 他全9名
  • Journal Title: J. Transl. Med Volume: 12(1) Issue: 1 Pages: 61-61
  • DOI: 10.1186/1479-5876-12-61
  • Peer Reviewed
• [Journal Article] Identification of an HLA-A2-restricted epitope peptide derived from hypoxia-inducible protein 2 (HIG2) (2014)
  • Author(s): Yoshimura S, Tsunoda T, Osawa R, 他全14名
  • Journal Title: PLoS ONE Volume: 9 (1) Issue: 1 Pages: e85267-e85267
  • DOI: 10.1371/journal.pone.0085267
  • Peer Reviewed / Open Access
• [Journal Article] A phase I clinical trial of vaccination with KIF20A-derived peptide in combination with gemcitabine for patients with advanced pancreatic cancer (2014)
  • Author(s): Suzuki N, Hazama S, Ueno T, 他全10名
  • Journal Title: J. Immunother Volume: 37 (1) Issue: 1 Pages: 36-42
  • DOI: 10.1097/cji.0000000000000012
  • Peer Reviewed
• [Journal Article] Immunological responses to a multi-target vaccine composed of peptides of cancer testis antigens and vascular endothelial growth factor receptors in patients with advanced pancreatic cancer (2013)
  • Author(s): Okuyama R, Aruga A, Hatori T,Takeda K, Yamamoto M
  • Journal Title: Onco Immunology Volume: 2(11) Issue: 11 Pages: e27010-e27010
  • DOI: 10.4161/onci.27010
  • Peer Reviewed
• [Journal Article] Phase I/II clinical trial using HLA-A24-restricted peptide vaccine derived from KIF20A for patients with advanced pancreatic cancer (2013)
  • Author(s): Asahara S, Takeda K, Yamao K, Maguchi H, Yamaue H
  • Journal Title: J. Transl. Med Volume: 11 Issue: 1 Pages: 291-291
  • DOI: 10.1186/1479-5876-11-291
  • Peer Reviewed
• [Journal Article] Long-term vaccination with multiple peptides derived from cancer-testis antigens can maintain a specific T-cell response and achieve disease stability in advanced biliary tract cancer (2013)
  • Author(s): Aruga A, Takeshita N, Kotera Y, 他全8名
  • Journal Title: Clin. Cancer Res. Volume: 19 (8) Issue: 8 Pages: 2224-2231
  • DOI: 10.1158/1078-0432.ccr-12-3592
  • Peer Reviewed
• [Journal Article] Functional roles of tumor necrosis factor-related apoptosis-inducing ligand-DR5 interaction in B16F10 cells by activating the nuclear factor-KB pathway to induce metastatic potential (2013)
  • Author(s): Kei Takahashi, Kazuyoshi Takeda, Ikuo Saiki, Tatsuro Irimura and Yoshihiro Hayakawa
  • Journal Title: Cancer Science Volume: 104 Issue: 5 Pages: 558-562
  • DOI: 10.1111/cas.12112
  • Peer Reviewed
• [Journal Article] Multiple therapeutic peptide vaccines consisting of combined novel cancer testis antigens and anti-angiogenic peptides for patients with non-small cell lung cancer (2013)
  • Author(s): Suzuki H, Fukuhara M, Yamaura T, 他全16名
  • Journal Title: J. Trans. Med Volume: 11(1) Issue: 1 Pages: 97-97
  • DOI: 10.1186/1479-5876-11-97
  • Peer Reviewed
• [Journal Article] Phase I clinical trial of a peptide vaccine combinated with tegafur-uracil plus leucovorin for treatment of advanced or recurrent colorectal cancer (2013)
  • Author(s): Matsusita N, Aruga A, Inoue Y, Kotera Y, Takeda K, Yamamoto M
  • Journal Title: Oncol. Rep Volume: 29 (3) Issue: 3 Pages: 951-959
  • DOI: 10.3892/or.2013.2231
  • Peer Reviewed
• [Journal Article] Local effects of regulatory T cells in MUC1 transgenic mice potentiate growth of MUC1 expressing tumor cells in vivo (2012)
  • Author(s): Sugiura D, Denda-Nagai K, Takashima M,他全7名
  • Journal Title: PLos One Volume: 7 (9) Issue: 9 Pages: e44770-e44770
  • DOI: 10.1371/journal.pone.0044770
  • Peer Reviewed
• [Journal Article] Phase I/II study of S-1 plus cisplatin combined with peptide vaccines for human vascular endothelial growth factor receptor 1 and 2 in patients with advanced gastric cancer (2012)
  • Author(s): Masuzawa T, Fujiwara Y, Okada K, 他全16名中
  • Journal Title: Int. J. Oncol Volume: 41 (4) Issue: 4 Pages: 1297-1304
  • DOI: 10.3892/ijo.2012.1573
  • Peer Reviewed
• [Journal Article] Identification of HLA-A24-restricted novel T cell epitope peptide derived from P-cadherin and kinesin family member 20A (2012)
  • Author(s): Osawa R, Tsunoda T, Yoshimura S, 他全10名
  • Journal Title: J. Biomed. Biotech Volume: 2012 Pages: 848042-848042
  • DOI: 10.1155/2012/848042
  • Peer Reviewed
• [Journal Article] Multicenter, phase II clinical trial of cancer vaccination for advanced esophageal cancer with three peptides derived from novel cancer-testis antigens. (2012)
  • Author(s): Kono K
  • Journal Title: J Transl Med Volume: 10（141） Issue: 1 Pages: 141-141
  • DOI: 10.1186/1479-5876-10-141
  • Peer Reviewed
• [Journal Article] Targeting spatiotemporal expression of CD137 on tumor-infiltrating cytotoxic T lymphocytes as a novel strategy for agonistic antibody therapy. (2012)
  • Author(s): Noji S, Hosoi A, Takeda K, Matsushita H, Morishita Y, Seto Y, Kakimi K.
  • Journal Title: J. Immunother Volume: 35(6) Issue: 6 Pages: 460-472
  • DOI: 10.1097/cji.0b013e31826092db
  • Peer Reviewed
• [Journal Article] Natural killer T cells suppress zymosan A-mediated granuloma formation in the liver by modulating interferon-γ and interleukin-10 (2012)
  • Author(s): Kobayashi T, Kawamura H, Kanda Y, 他全8名
  • Journal Title: Immunology Volume: 136(1) Pages: 86-95
  • Peer Reviewed
• [Journal Article] Cancer peptide vaccine therapy developed from oncoantigens identified through genome-wide expression profile analysis for bladder cancer (2012)
  • Author(s): Obara W, Ohsawa R, Kanehira M, 他全10名
  • Journal Title: Jpn. J. Clin. Oncol Volume: 42 (7) Issue: 7 Pages: 591-600
  • DOI: 10.1093/jjco/hys069
  • Peer Reviewed
• [Journal Article] Beta-glucosylceramide administration (i.p.) activates natural killer T cells in vivo and prevents tumor metastasis in mice. (2012)
  • Author(s): Inafuku, M.
  • Journal Title: Lipids Volume: 47 Issue: 6 Pages: 581-591
  • DOI: 10.1007/s11745-012-3666-1
  • Peer Reviewed
• [Journal Article] Significant clinical response of advanced colon cancer to peptide vaccine therapy: a case report. (2012)
  • Author(s): Yasuda, S.
  • Journal Title: Tokai J. Exp. Clin. Med. Volume: 37 Pages: 57-61
  • Peer Reviewed
• [Journal Article] Importin β1 protein-mediated nuclear localization of death receptor 5 (DR5) limits DR5/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced cell death of human tumor cells (2011)
  • Author(s): Kojima Y, Nakayama M, Nishina T, Nakano H, Koyanagi M, Takeda K, Okumura K, Yagita H
  • Journal Title: J Biol Chem Volume: 286 Issue: 50 Pages: 43383-43393
  • DOI: 10.1074/jbc.m111.309377
  • Peer Reviewed
• [Journal Article] Interaction between NK cells and dendritic cells generate MHC class II-dressed NK cells to regulate CD4^+ T cells (2011)
  • Author(s): Nakayama M, et al
  • Journal Title: Proc.Natl.Acad.Sci.USA Volume: 108 Issue: 45 Pages: 18360-18365
  • DOI: 10.1073/pnas.1110584108
  • Peer Reviewed
• [Journal Article] Early activation and interferon-Y production of tumor-infiltrating mature CD27 high natural killer cells (2011)
  • Author(s): Y.Hayakawa
  • Journal Title: Cancer Sci Volume: 102 Issue: 11 Pages: 1967-1971
  • DOI: 10.1111/j.1349-7006.2011.02042.x
  • Peer Reviewed
• [Journal Article] IFN-γ production by lung NK cells is sritical for the natural resistance to pulumonary metastasis of B16 melanoma in mice (2011)
  • Author(s): Takeda, K., Nakayama, M., et al
  • Journal Title: J.Leukoc.Biol. Volume: 90 Issue: 4 Pages: 777-785
  • DOI: 10.1189/jlb.0411208
  • Peer Reviewed
• [Journal Article] Tumor necrosis factor receptor-associated factor (TRAF) 2 control homeostasis of the colon to prevent spontaneous development of murine inflammatory bowel disease (2011)
  • Author(s): Piao, J.H., Hasegawa, M., et al
  • Journal Title: J.Biol.Chem. Volume: 286 Issue: 20 Pages: 17879-17888
  • DOI: 10.1074/jbc.m111.221853
  • Peer Reviewed
• [Journal Article] CD1d-restricted natural killer T cells contribute to hepatic inflammation and fibrogenesis in mice (2011)
  • Author(s): Ishikawa, S., Ikejima, K., et al
  • Journal Title: J.Hepatol. Volume: 54 Issue: 6 Pages: 1195-1204
  • DOI: 10.1016/j.jhep.2010.08.022
  • Peer Reviewed
• [Presentation] Pulripotents stem cell-derived myeloid cells engineered to express TRAIL as a possible cell medicine for cancer (2013)
  • Author(s): MAKI Hiroyuki
  • Organizer: 第42回日本免疫学会学術総会
  • Place of Presentation: 幕張
  • Year and Date: 2013-12-11
• [Presentation] A phase 1 clinical trial with KIF20A peptide in combination with gemcitabine for advanced pancreatic cancer patients (2013)
  • Author(s): 鈴木伸明
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2013-10-03
• [Presentation] Role of Neogenin in GD3- expressing human melanoma cells (2013)
  • Author(s): 折茂彰
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2013-10-03
• [Presentation] Role of Neogenin n GD3- expressing human melanoma cells.癌内線維芽細胞の近傍のヒト乳がん細胞に転移能を授ける (2013)
  • Author(s): 折茂彰、伊藤恭彦、竹田和由、奥村康、樋野興夫、堀本義哉
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 2) A phase 1 clinical trial with KIF20A peptide in combination with gemcitabine for advanced pancreatic cancer patients.切除不能・進行膵癌に対する新規膵癌ペプチドワクチンとゲムシタビン塩酸塩を用いた第1相試験 (2013)
  • Author(s): 鈴木伸明、硲彰一、上野富雄、吉野茂文、竹田和由、中村祐輔、岡正朗
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 3) Pulripotents stem cell-derived myeloid cells engineered to express TRAIL as a possible cell medicine for cancer. TRAILを発現する多機能幹細胞由来ミエロイド細胞を用いた細胞医薬の開発 (2013)
  • Author(s): 牧寛之、植村靖史、張エイ、竹田和由、劉天懿、鈴木元晴、都築忍、岡村文子、赤塚美樹、西村泰治、千住覚、葛島清隆
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 4) Pulripotents stem cell-derived myeloid cells engineered to express TRAIL as a possible cell medicine for cancer. (2013)
  • Author(s): MAKI Hiroyuki,UEMURA Yasushi, AHANG Rong, LIU Tianyi, SUZUKI Motoharu, HIROSAW Natsumi, TAKEDA Kazuyoshi, SAKAMOTO Yasushi, SENJU Satoru, KUZUSHIMA Kiyotaka
  • Organizer: 第42回日本免疫学会学術総会
  • Place of Presentation: 幕張
• [Presentation] Trogocytosis- mediated generation of regulatory MHCII-dressed NK cells (2012)
  • Author(s): NAKAYAMA Masafumi
  • Organizer: 第41回日本免疫学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-07
• [Presentation] The discriminatory activation of tumor specific cytotoxic T lymphocytes localized in the tumor by anti-4-1 BB mAb (2011)
  • Author(s): HOSOI Akihiko
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 幕張
  • Year and Date: 2011-11-28
• [Presentation] The discriminatory activation of tumor specific cytotoxic T lymphocytes localized in the tumor by anti-4-1 BB mAb (2011)
  • Author(s): 細井亮宏
  • Organizer: 日本免疫学会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2011-11-28
• [Presentation] NK-dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4+ T cells (2011)
  • Author(s): NAKAYAMA Masafumi
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 幕張
  • Year and Date: 2011-11-27
• [Presentation] NK-dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4+ T cells (2011)
  • Author(s): 中山勝文
  • Organizer: 日本免疫学会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2011-11-27
• [Remarks]
  • URL: http://www.juntendo.ac.jp/graduate/laboratory/labo/meneki/index.html