Enhanced in vivo growth of lymphoma tumors in the absence of the NK-activating receptor NKp46/NCR1

Gili G. Halfteck, Moran Elboim, Chamutal Gur, Hagit Achdout, Hormas Ghadially, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

119 Scopus citations


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 Ncr1gfp/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.

Original languageAmerican English
Pages (from-to)2221-2230
Number of pages10
JournalJournal of Immunology
Issue number4
StatePublished - 15 Feb 2009


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