Open AccessAnticancer efficacy of monotherapy with antibodies to SIRPα/SIRPβ1 mediated by induction of antitumorigenic macrophages
Author(s) -
Mariko Sakamoto,
Yoji Murata,
Daisuke Tanaka,
Yuka Kakuchi,
Takeshi Okamoto,
Daisuke Hazama,
Yasuyuki Saito,
Takenori Kotani,
Hiroshi Ohnishi,
Masayuki Miyasaka,
Masato Fujisawa,
Takashi Matozaki
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2109923118
Subject(s) - antibody , immunology , cancer research , biology , medicine
Significance Tumor-infiltrating macrophages are involved in tumor development, progression, and metastasis. Much recent attention has focused on the modification of macrophage functions in tumors as a basis for cancer treatments. SIRPα and SIRPβ1 are present in macrophages and function as a regulator for phagocytosis. We found that monotherapy with an anti-SIRPα/SIRPβ1 antibody (Ab) suppresses tumor formation by bladder and mammary cancer cells in mice. This effect is likely mediated by promoting the cytotoxic and phagocytic activity of macrophages against tumor cells. Notably, the antitumor effect of the Ab is largely dependent on its binding to SIRPβ1 on macrophages. Our findings reveal mechanisms of antitumor action of the anti-SIRPα/SIRPβ1 Ab and targeting of SIRPβ1 as a potential strategy for cancer immunotherapy.