Ficolin-2 triggers antitumor effect by activating macrophages and CD8+ T cells

被引:15
作者
Ding, Quanquan [1 ,2 ,3 ]
Shen, Yanying [1 ,2 ,3 ]
Li, Dongqing [4 ]
Yang, Juan [1 ,2 ,3 ]
Yu, Jing [5 ]
Yin, Zhinan [6 ]
Zhang, Xiao-Lian [1 ,2 ,3 ]
机构
[1] Wuhan Univ, State Key Lab Virol, Sch Basic Med Sci, Wuhan 430071, Hubei, Peoples R China
[2] Wuhan Univ, Med Res Inst, Sch Basic Med Sci, Hubei Prov Key Lab Allergy & Immunol, Wuhan 430071, Hubei, Peoples R China
[3] Wuhan Univ, Dept Immunol, Sch Basic Med Sci, Wuhan 430071, Hubei, Peoples R China
[4] Wuhan Univ, Dept Microbiol, Sch Basic Med Sci, Wuhan 430071, Hubei, Peoples R China
[5] Hubei Prov Canc Hosp, Wuhan 430079, Hubei, Peoples R China
[6] Jinan Univ, Biomed Translat Res Inst, Guangzhou 510630, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Ficolin-2/A; Antitumor effect; Macrophage; Dendritic cells (DCs); CD8(+) T; VIRUS-INFECTION; INNATE IMMUNITY; IN-VIVO; TUMOR MICROENVIRONMENT; CANCER; INFLAMMATION; BINDING; LIVER; IMMUNOTHERAPY; POLARIZATION;
D O I
10.1016/j.clim.2017.08.012
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Ficolin-2 is an important serum complement lectin. Here, we describe novel findings indicating that serum ficolin-2 concentrations in multiple tumor patients are significantly lower than those in healthy donors. Administration of exogenous ficolin-2 or ficolin-A (a ficolin-2-like molecule in mouse), with only once, could remarkably inhibit the tumor cells growth in murine tumor models via early macrophages, dendritic cells (DCs) and CD8(+) T cells, but not CD4(+) T cells. Ficolin-A (FCN-A) knockout (KO) mice exhibits significantly increased tumor cell growth. Ficolin-2 induces macrophage activation, promotes M1 polarization and facilitates proliferation and antigen-specific cytotoxicity of CD8(+) T cells. Ficolin-2 binds to Toll-like receptor 4 (TLR4) on macrophages and DCs and promotes their antigen-presenting abilities to CD8(+) T cells. Our findings provide a new therapeutic strategy for tumors based on the triggering of immune-mediated antitumor effect by ficolin-2. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码:145 / 157
页数:13
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