The CD47-SIRPa signaling blockade accelerates macrophage phagocytic activity against cancer cells

2013 Fiscal Year Final Research Report

• Project/Area Number: 23249064
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Hiroshima University
• Principal Investigator: OHDAN Hideki 広島大学, 医歯薬保健学研究院, 教授 (10363061)
• Co-Investigator(Kenkyū-buntansha): IDE Kentaro 広島大学, 大学病院, 病院助教 (50511565) ; KOBAYASHI Takaaki 名古屋大学, 医学系(医)研究科(研究院), 寄付講座教授 (70314010) ; TAHARA Hidetoshi 広島大学, 医歯薬保健学研究院, 教授 (00271065) ; SHIMAMOTO Akira 広島大学, 医歯薬保健学研究院, 准教授 (70432713) ; TANAKA Yuka 広島大学, 医歯薬保健学研究院, 助教 (90432666)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 腫瘍免疫 / 免疫回避

Research Abstract

We investigated whether inhibition of CD47-SIRPa signaling increases macrophage phagocytic activity against cancer cells by using in vitro and in vivo mouse syngeneic models. CD47 knock down Hepa1-6 cells were significantly more sensitive to macrophage phagocytosis than parental Hepa1-6 cells in both of in vitro and in vivo phagocytosis assays, indicating the pivotal role of CD47-SIRPa interaction in restricting tumor cell killing. Addition of anti-SIRPa mAns markedly enhanced the phagocytic activity of peritoneal cavity macrophage against Hepa1-6 and CMT93 compared with the isotype-matched Ab treatment in both of the in vitro and in vivo phagocytosis assays. Thus, our results suggest that CD47-SIRPa signaling interaction is a therapeutic target for inhibiting the growth of cancer cells.

Research Products

• [Journal Article] Prevention of recurrence after curative treatment for hepatocellular carcinoma (2013)
  • Author(s): Kobayashi T, Ishiyama K, Ohdan H
  • Journal Title: Surg Today Volume: 43(12) Pages: 1347-54
  • DOI: 10.1007/s00595-012-0473-5
  • Peer Reviewed
• [Journal Article] Expression of recipient CD47 on rat insulinoma cell xenografts prevents macrophage-mediated rejection through SIRPα inhibitory signaling in mice (2013)
  • Author(s): Teraoka Y, Ide K, Morimoto H, Tahara H, Ohdan H
  • Journal Title: PLoS One Volume: 8(3) Pages: e58359
  • DOI: 10.1371/journal.pone.0058359
  • Peer Reviewed
• [Journal Article] Mechanistic analysis of the antitumor efficacy of TRAIL-positive human natural killer cells (2012)
  • Author(s): Kajitani K, Tanaka Y, Ohdan H, Arihiro K, Kataoka T
  • Journal Title: Nihon Rinsho Volume: 7 Pages: 208-13
• [Presentation] The CD47-signaling regulatory protein alpha (SIRPα ) signaling blockade enhances macrophage phagocytic activity against cancer cells (2014)
  • Author(s): Tomoyuki Abe, Yuka Tanaka, Piao Jinlian, Naoki Tanimine, Kentaro Ide, Hideki Ohdan
  • Organizer: Transplant Congress
  • Place of Presentation: San Francisco, USA
  • Year and Date: 20140726-31
• [Presentation] The therapeutic targeting the CD47-signaling regulatory protein alpha 020004000600080001 00001 20001 40001 6000 φ only isotype control anti-CD47mAb anti-SIRPa mAb combined mAbs 2hr図Cellnumbers 5 . ト ラ ンス ウ ェ ルを 用 いたマ ウ ス 腹腔内マ ク ロファ ージ migration assay図6 . 大腸癌自 然発生マウ ス モデル(Cpc/Apc マウ ス ) を用いた抗 SIRPα 抗体の腫瘍増勢に与える 経時的変化501 01 5202530359wks 1 6wks 20wks 24wks 28wks isotype control Ab anti-SIRPa Ab p=0.05 p<0.05総腫瘍径(SIRPα ) signaling inhibition enhances macrophage phagocytic activity against cancer cells (2014)
  • Author(s): Tomoyuki Abe, Yuka Tanaka, Piao Jinlian, Naoki Tanimine, Kentaro Ide, Hideki Ohdan
  • Organizer: 第22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: 神戸
  • Year and Date: 20140602-03
• [Presentation] CD47-SIRPαシグナル遮断によるマクロファージ抗腫瘍活性の増強 (2014)
  • Author(s): 安部智之, 田 中友加, 谷峰直樹, 朴 金連, 矢野琢也, 坂井寛, 佐伯吉弘, 清水誠一,森本博司, 平田 文宏, 橋本慎二, 大平真裕,田 原裕之, 井手健太郎, 石山宏平, 小林剛,田 代裕尊, 大段秀樹
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 京都
  • Year and Date: 20140403-05
• [Presentation] The CD47-SIRPα signaling blockade accelerates macrophage phagocytic activity against hepatocellular carcinoma even under immunosuppressive conditions (2013)
  • Author(s): Tomoyuki Abe, Yuka Tanaka, Piao Jinlian, Naoki Tanimine, Kentaro Ide, Hideki Ohdan
  • Organizer: 3rd ESOT Basic Science Meeting
  • Place of Presentation: Paris, France
  • Year and Date: 20131103-05
• [Presentation] The CD47-SIRPα signaling inhibition enhances macrophage phagocytic activity against hepatocellular carcinoma (2013)
  • Author(s): Tomoyuki Abe, Yuka Tanaka, Paku Kinren, Naoki Tanimine, Kentaro Ide, Hideki Ohdan
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20131003-05
• [Presentation] CD47-SIRPαシグナルを介した癌細胞免疫回避機構の解明とその制御法の開発 (2013)
  • Author(s): 安部智之, 田 中友加, 谷峰直樹, 朴 金連, 井手健太郎, 佐伯吉弘, 清水誠一, 森本博司, 平田文宏, 橋本慎二, 山下正博, 堀田龍一, 寺岡義布史, 田澤宏文, 石山宏平, 田代裕尊, 大段秀樹
  • Organizer: 第31回日本肝移植研究会
  • Place of Presentation: 熊本
  • Year and Date: 20130704-05
• [Presentation] Blocking CD47-SIRPα signaling promotes the phagocytic activity of macrophages against hepatocellular carcinoma (2013)
  • Author(s): Tomoyuki Abe, Yuka Tanaka, Piao Jinlian, Naoki Tanimine, Kentaro Ide, Hideki Ohdan
  • Organizer: 14th American Transplant Congress
  • Place of Presentation: Seattle, USA
  • Year and Date: 20130518-22
• [Presentation] CD47-SIRPαシグナルを介した癌細胞の免疫回避機構におけるマクロファージの役割 (2013)
  • Author(s): 安部智之, 田 中友加, 谷峰直樹, 朴 金連, 佐伯吉弘, 清水誠一, 森本博司, 平田文宏, 橋本慎二, 山下正博, 堀田龍一, 寺岡義布史, 田澤宏文, 井手健太郎, 石山宏平, 田代裕尊, 大段秀樹
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡
  • Year and Date: 20130411-13
• [Presentation] Blocking CD47-SIRPα signaling enhances the phagocytic activity of liver-resident macrophages against hepatocellular carcinoma (2012)
  • Author(s): Tomoyuki Abe, Yuka Tanaka, Piao Jinlian, Naoki Tanimine, Kentaro Ide, Hideki Ohdan
  • Organizer: 13th American Transplant Congress
  • Place of Presentation: Boston, USA
  • Year and Date: 20120602-06