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

ABSTRACT: 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.

SUBMITTER: Deng W

PROVIDER: S-EPMC4856222 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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

Deng Weiwen W Gowen Benjamin G BG Zhang Li L Wang Lin L Lau Stephanie S Iannello Alexandre A Xu Jianfeng J Rovis Tihana L TL Xiong Na N Raulet David H DH

Science (New York, N.Y.) 20150305 6230

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 ...[more]

PMID: 25745066

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