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

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.

journal_name

Hum Immunol

journal_title

Human immunology

authors

Lesport E,Baudhuin J,LeMaoult J,Sousa S,Doliger C,Carosella ED,Favier B

doi

10.1016/j.humimm.2009.07.019

subject

Has Abstract

pub_date

2009-12-01 00:00:00

pages

1000-5

issue

12

eissn

0198-8859

issn

1879-1166

pii

S0198-8859(09)00194-3

journal_volume

70

pub_type

杂志文章

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