Human melanoma cell secreting human leukocyte antigen–G5 inhibit natural killer cell cytotoxicity by impairing lytic granules polarization toward target cell

• Published in: Human immunology Vol. 70; no. 12; pp. 1000 - 1005
• Main Authors: Lesport, Emilie, Baudhuin, Jeremy, LeMaoult, Joel, Sousa, Sylvie, Doliger, Christelle, Carosella, Edgardo D, Favier, Benoit
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2009
• Subjects: Actins - immunology; Actins - metabolism; Allergy and Immunology; Cell Line, Tumor; Cytoplasmic Granules - immunology; Cytoplasmic Granules - metabolism; Cytotoxicity; Cytotoxicity, Immunologic - immunology; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; HLA Antigens - immunology; HLA Antigens - metabolism; HLA-G Antigens; HLA-G5; Humans; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Melanoma - immunology; Melanoma - metabolism; NK cell; Perforin - metabolism; Skin Neoplasms - immunology; Skin Neoplasms - metabolism; Target cell; Transfection; Tumor Escape; Cytotoxicity; Target cell; HLA-G5; NK cell
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2009.07.019

Abstract Human leukocyte antigen–G (HLA-G) is a nonclassical tolerogenic molecule that can be expressed either as membrane bound (HLA-G1) or secreted (HLA-G5) isoforms. Upregulation of HLA-G1 or HLA-G5 expression by tumor cells constitutes an efficient way to escape from antitumoral immune responses. The inhibitory role of HLA-G1 on NK cell cytotoxicity is well characterized; however, that of the HLA-G5 isoform secreted by tumor is poorly understood. Our results indicate that the HLA-G5 isoform secreted by M8 melanoma cells is able to protect them from natural killer leukemia cell line (NKL) cytotoxicity. Analysis of NKL/M8-HLA-G5 conjugates by confocal microscopy demonstrates that the inhibition of NKL cytotoxic activity resulted from an impairment of NKL actin reorganization and perforin granules polarization toward M8-HLA-G5 target cell. This study also indicates that HLA-G5 soluble isoform remains evenly distributed in the cytoplasm of M8-HLA-G5 conjugated to NKL cells, suggesting that HLA-G5 does not require to polarize toward effector cell to induce efficient inhibition. These results highlight the inhibitory mechanisms mediated through HLA-G5 leading to tumor escape from NK cell cytotoxicity.