Development of a novel tumor immunotherapy that targets the soluble poliovirus receptor

2012 Fiscal Year Final Research Report

• Project/Area Number: 22390073
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: University of Tsukuba
• Principal Investigator: SHIBUYA Kazuko 筑波大学, 医学医療系, 准教授 (00302406)
• Project Period (FY): 2010 – 2012
• Keywords: 免疫学 / 癌 / 生体分子 / 病理学

Research Abstract

An activated immune receptor, DNAM-1, on T cells and NK cells binds to membrane-type poliovirus receptor (PVR) expressed on tumor cells, resulting in the immune surveillance against carcinogenesis. On the other hand, we found that the soluble PVR produced from tumor cells was involved in the escape from immune surveillance by DNAM-1. These results suggest that the soluble PVR can potentially be a target for novel cancer therapy that inhibit an immune escape, enhancing tumor immune surveillance by DNAM-1.

Research Products

• [Journal Article] Establishment and Characterization of a Novel Anti-DNAM-1 Monoclonal Antibody (2013)
  • Author(s): Yamashita Y, Abe F, Hirochika R, Tahara-Hanaoka S, Shibuya A, Shibuya K.
  • Journal Title: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy Volume: 32(1) Pages: 60-64
  • DOI: DOI:10.1089/mab.2012.0083
  • Peer Reviewed
• [Journal Article] CD226 interaction with CD155 impacts on retention and negative selection of CD8 positive thymocytes as well as T cell differentiation to follicular helper cells in Peyer's Patches. (2013)
  • Author(s): Danisch S, Qiu Q, Seth S, Ravens I, Dorsch M, Shibuya A, Shibuya K, Forster R, Bernhardt G
  • Journal Title: Immunobiology Volume: 218 Pages: 152-158
  • Peer Reviewed
• [Journal Article] 急性GVHD発症における活性化免疫受容体DNAM-1の重要な役割 (2012)
  • Author(s): 金谷穣、鍋倉宰、渋谷和子、渋谷彰
  • Journal Title: 臨床血液 Volume: Vol.53、No.5 Pages: 497-503
• [Journal Article] Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor (2012)
  • Author(s): Nakahashi-Oda C, Tahara-Hanaoka S, Shoji M, Okoshi Y, Nakano-Yokomizo T, OhkohchiN, Yasui T, Kikutani H, Honda S, Shibuya K, Nagata S, Shibuya A.
  • Journal Title: J Exp Med Volume: 209(8) Pages: 1493-1503
  • DOI: DOI:10.1084/jem.20120096
  • Peer Reviewed
• [Journal Article] Overexpression of RORγt under control of the CD2 promoter induces polyclonal plasmacytosis and autoantibody production in transgenic mice (2012)
  • Author(s): Yoh K, Morito N, Ojima M, Shibuya K, Yamashita Y, Morishima Y, Ishii Y, Kusakabe M, Nishikii H, Fujita A, Matsunaga E, Okamura M, Hamada M, Suto A, Nakajima H, Shibuya A, Yamagata K, Takahashi S
  • Journal Title: Eur J Immunol Volume: 42 Pages: 1999-2009
  • DOI: DOI:10.1002/eji.201142250
  • Peer Reviewed
• [Journal Article] Identification of phosphatidylserine as a ligand for the CD300a immunoreceptor (2012)
  • Author(s): Nakahashi- Oda C, Tahara-Hanaoka S, Honda S, Shibuya K, Shibuya A
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 417 Pages: 646-650
  • DOI: DOI:10.1016/j.bbrc.2011.12.025
  • Peer Reviewed
• [Journal Article] Isolation and characterization of naive follicular dendritic cells (2012)
  • Author(s): Usui K, Honda S, Yoshizawa Y, Nakahashi-Oda C, Tahara- Hanaoka S, Shibuya K, Shibuya A
  • Journal Title: Mol Immunol Volume: 50 Pages: 172-176
  • DOI: DOI:10.1016/j.molimm.2011.11.010
  • Peer Reviewed
• [Journal Article] The immunoreceptor adapter protein DAP12 suppresses B lymphocyte-driven adaptive immune responses (2011)
  • Author(s): NakanoYokomizo T, Tahara-Hanaoka S, Nakahashi-Oda C, Nabekura T, Nadia K. Tchao, Kadosaki M, Totsuka N, Kurita N, Nakamagoe K, Tamaoka A, Takai T, Yasui T, Kikutani H, Honda S, Shibuya K, Lewis L. Lanier, Shibuya A
  • Journal Title: J Exp Med Volume: 1;208(8) Pages: 1661-1671
  • DOI: DOI:10.1084/jem.20101623
  • Peer Reviewed
• [Journal Article] Reply to Seth et al.: DNAX accessory molecule-1 (DNAM-1) plays an important role in alloreactive CD8+ T cells responsible for the exacerbation of acute graft-versus-host disease (2011)
  • Author(s): Nabekura T, Shibuya K, Shibuya A
  • Journal Title: Proc Natl Acad Sci USA Volume: 108(10)E34
  • DOI: DOI:10. 1073/pnas.1005582107
  • Peer Reviewed
• [Journal Article] ナチュラルキラー細胞 (2010)
  • Author(s): 鍋倉宰、渋谷和子、渋谷彰
  • Journal Title: 侵襲と免疫 Volume: Vol.19、No.2 Pages: 17-25
• [Journal Article] Critical role of DNAX accessory molecule-1 (DNAM-1) in the development of acute graft-versus-host disease in mice (2010)
  • Author(s): Nabekura T, Shibuya K, Takenaka E, Kai H, Shibata K, Yamashita Y, Harada K, Tahara-Hanaoka S, Honda S, Shibuya A
  • Journal Title: Proc Natl Acad Sci USA Volume: 107 Pages: 18593-18598
  • DOI: DOI:10.1073/pnas.1005582107
  • Peer Reviewed
• [Journal Article] An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E-mediated immediate hypersensitivity reactions. (2010)
  • Author(s): Hitomi K, Tahara-Hanaoka S, Someya S, Fujiki A, Tada H, Sugiyama T, Shibayama S, Shibuya K, Shibuya A
  • Journal Title: Nature Immunology Volume: 11 Pages: 601-607
  • DOI: DOI:10.1038/ni.1886
  • Peer Reviewed
• [Presentation] CD155 is a co-stimulatory molecule involved in Th1 development. (2013)
  • Author(s): 山下由美、高橋勇一、渋谷彰、渋谷和子
  • Organizer: 筑波大学・東京理科大学生命医科学研究所合同リトリート
  • Place of Presentation: 東京理科大学セミナーハウス, 野田
  • Year and Date: 2013-03-29
• [Presentation] CD155 mediates a costimulatory signal for Th1 development and is involved in the development of allergic diseases (2013)
  • Author(s): Yamashita Y, Takahashi Y, Abe F, Shibuya A, Shibuya K
  • Organizer: JST-CREST国際シンポジウムFrontiers in Immunology & Inflammation
  • Place of Presentation: 一橋記念講堂, 東京
  • Year and Date: 2013-02-12
• [Presentation] The paradoxical role of an immune receptor, DNAM-1, in tumor development. (2013)
  • Author(s): Shibuya K
  • Organizer: 第3回発がんスパイラル国際シンポジウム
  • Place of Presentation: 金沢エクセルホテル東急, 金沢
  • Year and Date: 2013-01-24
• [Presentation] Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor (2012)
  • Author(s): Nakhashi-Oda C, Tahara-Hanaoka S, Yasui T, Kikutani H, Honda S, Shibuya K, Nagata S, Shibuya A
  • Organizer: 第41回日本免疫学会国際シンポジウム
  • Place of Presentation: 神戸国際会議場, 兵庫
  • Year and Date: 2012-12-06
• [Presentation] Critical role of DNAM-1 in acute and chronic allograft rejection (2012)
  • Author(s): Abe F, Shibuya K, Shibuya A
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸国際会議場, 兵庫
  • Year and Date: 2012-12-05
• [Presentation] Critical role of activating immune receptor DNAM-1 in the development of acute hepatic GVHD (2012)
  • Author(s): Kanaya M, Shibuya K, Abe F, Shibuya. A
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸国際会議場, 兵庫
  • Year and Date: 2012-12-05
• [Presentation] CD155 is a co-stimulatory molecule involved in Th1 differentiation (2012)
  • Author(s): Yamashita Y, Takahashi Y, Wang Y, Abe F, Yoshioka A, Shibuya A, Shibuya K
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸国際会議場, 兵庫
  • Year and Date: 2012-12-05
• [Presentation] CD155 mediates a costimulatory signal for Th1 development and is involved in the development of allergic diseases (2012)
  • Author(s): Yamashita Y, Takahashi Y, Abe F, Shibuya A, Shibuya K
  • Organizer: The 7th Tsukuba Medical Science Research Meeting
  • Place of Presentation: Tsukuba International Congress Center., つくば
  • Year and Date: 2012-10-01
• [Presentation] 可溶型DNAM-1の急性GVHD発症予測マーカーとしての有用性 (2012)
  • Author(s): 金谷穣、広近玲、渋谷和子、岡田昌文、我妻ゆき子、坂巻壽、渋谷彰
  • Organizer: 第4回造血器腫瘍免疫療法研究会学術集会
  • Place of Presentation: 金沢市文化ホール, 金沢
  • Year and Date: 2012-08-18
• [Presentation] 活性化免疫受容体DNAM-1の急性肝GVHDの病態形成における重要な役割 (2012)
  • Author(s): 金谷穣、渋谷和子、阿部史枝、鍋倉宰、渋谷彰
  • Organizer: 第4回造血器腫瘍免疫療法研究会学術集会
  • Place of Presentation: 金沢市文化ホール, 金沢
  • Year and Date: 2012-08-18
• [Presentation] CD155 (poliovirus receptor)のTh1分化における役割と疾患への関与 (2012)
  • Author(s): 山下由美、高橋勇一、王軼楠、吉岡文、鍋倉宰、渋谷彰、渋谷和子
  • Organizer: 第22回Kyoto T Cell Conference
  • Place of Presentation: 和順会館, 京都
  • Year and Date: 2012-07-07
• [Presentation] Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor (2012)
  • Author(s): Nakhashi-Oda C, Tahara-Hanaoka S, Shibuya K, Shibuya A
  • Organizer: 9th International Conference on Innate Immunity
  • Place of Presentation: Ixia, Rhodes, Greece
  • Year and Date: 2012-06-27
• [Presentation] Iga/IgM受容体、Fcα/μ受容体の二量体形成の解析 (2011)
  • Author(s): 高垣香菜、本多伸一郎、臼井健太、吉澤勇一、渋谷和子、田原聡子、渋谷彰
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 幕張メッセ, 千葉
  • Year and Date: 2011-11-29
• [Presentation] ナイーブマウス脾臓からのFDCの単離 (2011)
  • Author(s): 臼井健太、本多伸一郎、吉澤勇一、田原聡子、渋谷和子、渋谷彰
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 幕張メッセ, 千葉
  • Year and Date: 2011-11-29
• [Presentation] MAIR-II (CD300d) on Ly-6Chigh inflammatory monocytes plays a crucial role in inflammatory responses in a murine sepsis model (2011)
  • Author(s): 戸塚直也、田原聡子、永井恵、小田(中橋)ちぐさ、人見香織、栗田尚樹、本多伸一郎、渋谷和子、渋谷彰
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 幕張メッセ, 千葉
  • Year and Date: 2011-11-29
• [Presentation] An immunoreceptor adapter protein, DAP12, suppresses adaptive immune responses mediated by B lymphocytes (2011)
  • Author(s): 小田(中橋)ちぐさ、田原聡子、安居輝人、菊谷仁、本多伸一郎、渋谷和子、長田重一、渋谷彰
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 幕張メッセ, 千葉
  • Year and Date: 2011-11-27
• [Presentation] The role of CD155, a noval co-stimulatory molecule in CD4+ T cell, in contact dermatitis (2011)
  • Author(s): 山下由美、Wang Yinan、吉岡文、鍋倉宰、田原聡子、本多伸一郎、渋谷彰、渋谷和子
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 幕張メッセ, 千葉
  • Year and Date: 2011-11-27
• [Presentation] A novel immunoglobulin-like receptor, Allergin-1, inhibits IgE-mediated allergic responses (2010)
  • Author(s): Tahara-Hanaoka S, Hitomi K, Someya S, Fujiki A, Tada H, Sugiyama T, Shibayama S, Shibuya K, Shibuya A
  • Organizer: CSHL Meeting-Gene Expression & Signaling in the Immune System
  • Place of Presentation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA
  • Year and Date: 20100421-25
• [Presentation] 免疫制御と治療.平成23年度日本免疫学会通常総会 (2010)
  • Author(s): 渋谷和子
  • Organizer: 2010年日本免疫学会シンポジウム
  • Place of Presentation: 一橋記念講堂, 東京
  • Year and Date: 2010-12-03
• [Presentation] Identification and characterization of the poliovirus receptor(CD155)as a novel co-stimulatory molecule in CD4+ T cells (2010)
  • Author(s): Yamashita Y, Wang Y, Yoshioka A, Nabekura T, Tahara-Hanaoka S, Honda S, Shibuya K, Shibuya A
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸国際会議場, 神戸
  • Year and Date: 2010-08-27
• [Presentation] A critical role of DNAM-1 in the development of acute graft-versus-host disease (2010)
  • Author(s): Nabekura T, Shibuya K, Takenaka E, Kai H, Shibata K, Yamashita Y, Harada K, Tahara-Hanaoka S, Honda S, Shibuya A
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸国際会議場, 神戸
  • Year and Date: 2010-08-26
• [Presentation] Regulation of serum IgA production by the Fcα/μR, an Fc receptor for IgA and IgM (2010)
  • Author(s): Honda S, Usui K, Yoshizawa Y, Takagaki K, Tahara-Hanaoka S, Shibuya K,Shibuya A
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸国際会議場, 神戸
  • Year and Date: 2010-08-26
• [Presentation] Decreased mortality in MAIR-I (CD300a) -deficient mice with experimental sepsis induced by cecal ligation and puncture (2010)
  • Author(s): Nakahashi-Oda C, Tahara-Hanaoka S, Shoji M, Totsuka N, Nakano T, Yasui T, Kikutani H, Shibuya K, Shibuya A
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸国際会議場, 神戸
  • Year and Date: 2010-08-24
• [Presentation] MAIR- II(CD300d)plays a crucial role in inflammatory responses in a murine sepsis model (2010)
  • Author(s): Totsuka N, Tahara-Hanaoka S, Nakahashi-Oda C, Kurita N, Nakano T, Yasui T, Kikutani H, Honda S, Shibuya K, Shibuya A
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸国際会議場, 神戸
  • Year and Date: 2010-08-24
• [Presentation] A novel immunoglobulin-like receptor, Allergin-1, inhibits IgE-mediated allergic responses (2010)
  • Author(s): Hitomi K, Tahara-Hanaoka S,Someya S, Shibuya K, Shibuya A
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸国際会議場, 神戸
  • Year and Date: 2010-08-23
• [Presentation] An immunoreceptor ando adaptor complex, MAIR- II/DAP12, negatively regulates B cell proliferation (2010)
  • Author(s): Nakano T, Tahara-Hanaoka S, Kadozaki M, Nakahashi-Oda C, Totsuka N, Yasui T, Kikutani H, Shibuya K, Lanier L L, Shibuya A
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸国際会議場, 神戸
  • Year and Date: 2010-08-23
• [Presentation] DNAM-1は移植片対宿主病の発症において重要な役割を果たす (2010)
  • Author(s): 鍋倉宰、渋谷和子、竹中江里、渋谷彰
  • Organizer: 第20回Kyoto T Cell Conference
  • Place of Presentation: 京都大学芝蘭会館, 京都
  • Year and Date: 2010-06-05
• [Remarks] ホームページ
  • URL: http://immunologylab-tsukuba.org/
• [Patent(Industrial Property Rights)] 免疫疾患に対する医薬組成物 (2013)
  • Inventor(s): 渋谷和子、渋谷彰、山下由美
  • Industrial Property Rights Holder: 筑波大学
  • Industrial Property Number: 出願 2013-050403
  • Filing Date: 2013-03-13
• [Patent(Industrial Property Rights)] 同種間での移植心臓、移植血管、または移植腎臓の生着を維持するために用いられる薬剤 (2012)
  • Inventor(s): 渋谷彰、渋谷和子、阿部史枝
  • Industrial Property Rights Holder: 筑波大学
  • Industrial Property Number: 出願 2012-117542
  • Filing Date: 2012-05-23