Downregulation of neuropilin-1 on macrophages modulates antibody-mediated tumoricidal activity
Downregulation of neuropilin-1 on macrophages modulates antibody-mediated tumoricidal activity
复制标题
DOI：
10.1007/s00262-017-2002-2
复制
发表时间：
2017-09-01
影响因子：
5.8
通讯作者：
Toi, Masakazu
中科院分区：
文献类型：
--
作者：
Kawaguchi, Kosuke;Suzuki, Eiji;Toi, Masakazu
表达神经纤毛蛋白-1（NRP-1）的巨噬细胞通过各种机制参与抗肿瘤免疫功能。在这项研究中，我们研究了NRP-1在抗体介导的杀肿瘤活性中对巨噬细胞的作用。用NRP-1敲低或抗NRP-1中和抗体处理巨噬细胞在体外显著抑制抗体依赖性细胞毒性并调节巨噬细胞的细胞因子分泌。此外，使用携带人表皮生长因子受体-2（HER 2）阳性乳腺癌异种移植物的人源化小鼠模型的体内研究显示，当NRP-1被敲低的外周血单核细胞与抗HER 2抗体共同给药时，抗体介导的抗肿瘤活性和CD 4（+）T淋巴细胞的肿瘤浸润显著下调。这些结果表明，在巨噬细胞上表达的NRP-1在抗体介导的抗肿瘤免疫中起重要作用。总之，巨噬细胞上NRP-1的诱导可能是发挥抗体依赖性细胞毒性活性的抗体治疗的治疗指标，尽管需要进一步的研究来支持这一假设。
Neuropilin-1 (NRP-1)-expressing macrophages are engaged in antitumor immune functions via various mechanisms. In this study, we investigated the role of NRP-1 on macrophages in antibody-mediated tumoricidal activity. Treatment of macrophages with NRP-1 knockdown or an anti-NRP-1-neutralizing antibody significantly suppressed antibody-dependent cellular cytotoxicity and modulated cytokine secretion from macrophages in vitro. Furthermore, in vivo studies using a humanized mouse model bearing human epidermal growth factor receptor-2 (HER2)-positive breast cancer xenografts showed that antibody-mediated antitumor activity and tumor infiltration of CD4(+) T lymphocytes were significantly downregulated when peripheral blood mononuclear cells in which NRP-1 was knocked down were co-administered with an anti-HER2 antibody. These results revealed that NRP-1 expressed on macrophages plays an important role in antibody-mediated antitumor immunity. Taken together, the induction of NRP-1 on macrophages may be a therapeutic indicator for antibody treatments that exert antibody-dependent cellular cytotoxicity activity, although further studies are needed in order to support this hypothesis.