Tumor immunoediting by NKp46.
NK cells interact with a wide variety of hazardous cells including pathogen-infected and tumor cells. NKp46 is a specific NK killer receptor that recognizes various influenza hemagglutinins and unknown tumor ligands. It was recently shown that NKp46 plays a significant role in the in vivo eradication of tumor cells; however, the role played by NKp46 in vivo with regard to tumor development is still unclear. In this study, we used the 3-methylcholanthrene (MCA)-induced fibrosarcoma model in NKp46-deficient mice to test the NKp46 recognition of carcinogen-induced tumors. We show that although the rate of MCA-induced tumor formation was similar in the presence and in the absence of NKp46, the expression of its unknown ligands was NKp46 dependent. The unknown NKp46 ligands were nearly absent in tumors that originated in wild-type mice, whereas they were detected in tumors that originated in the NKp46-deficient mice. We demonstrate that the interactions between NKp46 and its MCA tumor-derived ligands lead to the secretion of IFN-gamma but not to the elimination of the MCA-derived tumor cells. In addition, we show that the in vivo growth of MCA-derived tumor cells expressing high levels of the NKp46 ligands is NKp46 and IFN-gamma dependent. Thus, we present in this study a novel NKp46-mediated mechanism of tumor editing.
Elboim
Moran
M
Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Gazit
Roi
R
Gur
Chamutal
C
Ghadially
Hormas
H
Betser-Cohen
Gili
G
Mandelboim
Ofer
O
D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019556:COS Cells; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D018920:Coculture Techniques; D005354:Fibrosarcoma / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D007157:Immunologic Surveillance; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008024:Ligands; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019139:Tumor Escape / Q000276:immunology
D000950:Antigens, Ly; D008024:Ligands; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse; D008748:Methylcholanthrene; D007371:Interferon-gamma