Enhanced in vivo growth of lymphoma tumors in the absence of the NK-activating receptor NKp46/NCR1.
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.
Halfteck
Gili G
GG
Lautenberg Center for General and Tumor Immunology, The Hebrew University, Hadassah Medical School, Jerusalem, Israel.
Elboim
Moran
M
Gur
Chamutal
C
Achdout
Hagit
H
Ghadially
Hormas
H
Mandelboim
Ofer
O
D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005434:Flow Cytometry; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D008223:Lymphoma / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000235:genetics / Q000276:immunology*
D000950:Antigens, Ly; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse