A shed NKG2D ligand that promotes natural killer cell activation and tumor rejection

被引：206

作者：

Deng, Weiwen ^{[1
,2
]}

Gowen, Benjamin G. ^{[1
,2
]}

Zhang, Li ^{[1
,2
]}

Wang, Lin ^{[1
,2
]}

Lau, Stephanie ^{[1
,2
]}

Iannello, Alexandre ^{[1
,2
]}

Xu, Jianfeng ^{[1
,2
]}

Rovis, Tihana L. ^{[3
]}

Xiong, Na ^{[4
]}

Raulet, David H. ^{[1
,2
]}

机构：

[1] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

[2] Univ Calif Berkeley, Canc Res Lab, Berkeley, CA 94720 USA

[3] Univ Rijeka, Fac Med, Ctr Prote, Rijeka 51000, Croatia

[4] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA

来源：

SCIENCE | 2015年 / 348卷 / 6230期

基金：

美国国家科学基金会;

关键词：

IN-VIVO; EXPRESSION; NK; CYTOTOXICITY; RESPONSES; RECEPTOR; MOLECULES; EXOSOMES; RELEASE; NKP46;

D O I：

10.1126/science.1258867

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Immune cells, including natural killer (NK) cells, recognize transformed cells and eliminate them in a process termed immunosurveillance. It is thought that tumor cells evade immunosurveillance by shedding membrane ligands that bind to the NKG2D-activating receptor on NK cells and/or T cells, and desensitize these cells. In contrast, we show that in mice, a shed form of MULT1, a high-affinity NKG2D ligand, causes NK cell activation and tumor rejection. Recombinant soluble MULT1 stimulated tumor rejection in mice. Soluble MULT1 functions, at least in part, by competitively reversing a global desensitization of NK cells imposed by engagement of membrane NKG2D ligands on tumor-associated cells, such as myeloid cells. The results overturn conventional wisdom that soluble ligands are always inhibitory and suggest a new approach for cancer immunotherapy.

引用

页码：136 / 139

页数：4

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