Enhanced in vivo growth of lymphoma tumors in the absence of the NK-activating receptor NKp46/NCR1.
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| Abstract |
The in vitro elimination of virus-infected and tumor cells by NK cells is regulated by a balance between signals conveyed via specific inhibitory and activating receptors. Whether NK cells and specifically the NK-activating receptor NKp46 (NCR1 in mice) are directly involved in tumor eradication in vivo is still largely unknown. Since the NKp46/NCR1 tumor ligands have not been identified yet, we use a screening technique to identify functional ligands for NKp46/NCR1 which is based on a cell reporter assay and discover a NCR1 ligand in the PD1.6 lymphoma line. To study whether NKp46/NCR1 is important for the eradication of PD1.6 lymphoma in vivo, we used the Ncr1 knockout Ncr1(gfp/gfp) mice generated by our group. Strikingly, all Ncr1 knockout mice developed growing PD1.6 tumors, whereas initial tumor growth was observed in the wild-type mice and tumors were completely rejected as time progressed. The growth of other lymphoma cell lines such as B10 and EL4 was equivalent between the Ncr1 knockout and wild-type mice. Finally, we show that PD1.6 lymphoma cells are less killed both in vitro and in vivo in the absence of NKp46/NCR1. Our results therefore reveal a crucial role for NKp46/NCR1 in the in vivo eradication of some lymphoma cells.
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| Authors | Gili G Halfteck, Moran Elboim, Chamutal Gur, Hagit Achdout, Hormas Ghadially, Ofer Mandelboim |
| Journal | Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 182 Issue 4 Pg. 2221-30 (Feb 15 2009) ISSN: 1550-6606 [Electronic] United States |
| PMID | 19201876 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.) |
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