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

我们通过体外和体内小鼠同基因模型研究了CD47-SIRPa信号的抑制是否会增加巨噬细胞对癌细胞的吞噬活性。在体外和体内吞噬实验中，CD47敲低Hepa1-6细胞对巨噬细胞吞噬的敏感性明显高于亲本Hepa1-6细胞，这表明CD47- sirpa相互作用在限制肿瘤细胞杀伤方面具有关键作用。在体外和体内的吞噬实验中，与同型匹配的Ab处理相比，添加抗sirpa mAns显著增强了腹腔巨噬细胞对Hepa1-6和CMT93的吞噬活性。因此，我们的研究结果表明，CD47-SIRPa信号相互作用是抑制癌细胞生长的治疗靶点。

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.