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

Weiwen Deng, Benjamin G. Gowen, Li Zhang, Lin Wang, Stephanie Lau, Alexandre Iannello, Jianfeng Xu, Tihana L. Rovis, Na Xiong, David H. Raulet

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish (US)
Pages (from-to)136-139
Number of pages4
JournalScience
Volume348
Issue number6230
DOIs
StatePublished - Apr 3 2015

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Cite this

Deng, W., Gowen, B. G., Zhang, L., Wang, L., Lau, S., Iannello, A., Xu, J., Rovis, T. L., Xiong, N., & 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