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Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Science 2015 ; 348 (6230): 136-9 Nephropedia Template TP
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A shed NKG2D ligand that promotes natural killer cell activation and tumor rejection #MMPMID25745066
Deng W; Gowen BG; Zhang L; Wang L; Lau S; Iannello A; Xu J; Rovis TL; Xiong N; Raulet DH
Science 2015[Apr]; 348 (6230): 136-9 PMID25745066show ga
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, shedding 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 inhibitory, and suggest a new approach for cancer immunotherapy.