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

CD47-SIRPa信号传导阻断加速巨噬细胞对癌细胞的吞噬活性

• 批准号: 23249064
• 负责人: OHDAN Hideki
• 金额: $ 30.87万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23249064/
• 关键词: 腫瘍免疫; 免疫回避; 分子標的治療; 糖鎖抗原

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.

我们通过使用体外和体内小鼠同基因模型研究了抑制CD 47-SIRPa信号传导是否增加巨噬细胞对癌细胞的吞噬活性。在体外和体内吞噬测定中，CD 47敲低的Hepa 1 -6细胞比亲本Hepa 1 -6细胞对巨噬细胞吞噬作用显著更敏感，表明CD 47-SIRPa相互作用在限制肿瘤细胞杀伤中的关键作用。在体外和体内吞噬试验中，与同种型匹配的Ab处理相比，添加抗SIRPa mAns显著增强腹腔巨噬细胞对Hepa 1 -6和CMT 93的吞噬活性。因此，我们的结果表明，CD 47-SIRPa信号相互作用是抑制癌细胞生长的治疗靶点。

项目成果

Blocking CD47-SIRPα signaling enhances the phagocytic activity of liver-resident macrophages against hepatocellular carcinoma

阻断 CD47-SIRPα 信号传导可增强肝脏巨噬细胞对肝细胞癌的吞噬活性

• 发表时间: 2012
• 作者: Tomoyuki Abe;Yuka Tanaka;Piao Jinlian;Naoki Tanimine;Kentaro Ide;Hideki Ohdan
• 通讯作者: Hideki Ohdan

Genetic Induction of Recipient CD47 on Xenografts Prevents Macrophage-Mediated Rejection through CD47-SIRPα Inhibitory Signaling: Evidence from an In Vivo Xenograft Model.

异种移植物上受体 CD47 的基因诱导通过 CD47-SIRPα 抑制信号防止巨噬细胞介导的排斥反应：来自体内异种移植物模型的证据。

• 发表时间: 2012
• 作者: Teraoka Y;Teraoka Y;Ide K;Morimoto H;Ohdan H.
• 通讯作者: Ohdan H.

Tumor-related factors do not influence the prognosis of solitary hepatocellular carcinoma after partial hepatectomy

• DOI: 10.1007/s00534-011-0379-4
• 发表时间: 2011-03
• 期刊: Journal of Hepato-Biliary-Pancreatic Sciences
• 影响因子: 3
• 作者: Tsuyoshi Kobayashi;T. Itamoto;H. Tashiro;H. Amano;A. Oshita;Yoshisato Tanimoto;S. Kuroda;H. Tazawa;H. Ohdan

Mechanistic analysis of the antitumor efficacy of human natural killer cells against breast cancer cells

• DOI: 10.1007/s10549-011-1944-x
• 发表时间: 2012-07-01
• 期刊: BREAST CANCER RESEARCH AND TREATMENT
• 影响因子: 3.8
• 作者: Kajitani, Keiko;Tanaka, Yuka;Ohdan, Hideki
• 通讯作者: Ohdan, Hideki

Expression of recipient CD47 on rat insulinoma cell xenografts prevents macrophage-mediated rejection through SIRPα inhibitory signaling in mice.

• DOI: 10.1371/journal.pone.0058359
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Teraoka Y;Ide K;Morimoto H;Tahara H;Ohdan H
• 通讯作者: Ohdan H