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01-09-2017 | Original Article

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

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

Published in: Cancer Immunology, Immunotherapy | Issue 9/2017

Abstract

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.

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Title: Downregulation of neuropilin-1 on macrophages modulates antibody-mediated tumoricidal activity
Authors: Kosuke Kawaguchi
Eiji Suzuki
Mariko Nishie
Isao Kii
Tatsuki R. Kataoka
Masahiro Hirata
Masashi Inoue
Fengling Pu
Keiko Iwaisako
Moe Tsuda
Ayane Yamaguchi
Hironori Haga
Masatoshi Hagiwara
Masakazu Toi
Publication date: 01-09-2017
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 9/2017
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-017-2002-2

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