Downregulation of neuropilin-1 on macrophages modulates antibody-mediated tumoricidal activity

作者：Kawaguchi Kosuke; Suzuki Eiji^*; Nishie Mariko; Kii Isao; Kataoka Tatsuki R; Hirata Masahiro; Inoue Masashi; Pu Fengling; Iwaisako Keiko; Tsuda Moe; Yamaguchi Ayane; Haga Hironori; Hagiwara Masatoshi; Toi Masakazu

来源：Cancer Immunology, Immunotherapy, 2017, 66(9): 1131-1142.

DOI：10.1007/s00262-017-2002-2

• Neuropilin-1
• Breast cancer
• HER2
• Humanized mouse
• Antibody-dependent cellular cytotoxicity

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.

• 出版日期2017-9