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 Tcells, 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.
CITATION STYLE
Deng, W., Gowen, B. G., Zhang, L., Wang, L., Lau, S., Iannello, A., … Raulet, D. H. (2015). A shed NKG2D ligand that promotes natural killer cell activation and tumor rejection. Science, 348(6230), 136–139. https://doi.org/10.1126/science.1258867
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