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Science. 2015 Apr 3;348(6230):136-9. doi: 10.1126/science.1258867. Epub 2015 Mar 5.

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

Author information

1
Department of Molecular and Cell Biology, and Cancer Research Laboratory, University of California at Berkeley, Berkeley, CA 94720, USA.
2
Center for Proteomics University of Rijeka Faculty of Medicine Brace Branchetta 20, 51000 Rijeka, Croatia.
3
Department of Veterinary and Biomedical Sciences, Pennsylvania State University, 115 Henning Building, University Park, PA 16802, USA.
4
Department of Molecular and Cell Biology, and Cancer Research Laboratory, University of California at Berkeley, Berkeley, CA 94720, USA. raulet@berkeley.edu.

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.

PMID:
25745066
PMCID:
PMC4856222
DOI:
10.1126/science.1258867
[Indexed for MEDLINE]
Free PMC Article

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