HLA-G expressing NK cell subset with suppressive properties is expanded in breast cancer (TUM10P.1043)

Abstract NK cells were considered traditionally as cytotoxic effector cells rapidly killing infected and transformed cells. Recently, NK cells have been shown to act as potential regulatory cells interacting with various components of the immune system. HLA-G is an important immune-regulatory molecule.There is evidence that HLA-G expression contributes to escape of malignant cells from immune recognition and destruction by down-regulation of the immune response. Immunosuppressive T cells expressing HLA-G have been recently reported. In healthy donors, we have found a subset of circulating NK cells that constitutively express HLA-G (4.5±1.3, n=11), which occurs more frequently among CD57- than CD57+ NK cells. They are enhanced in response to PHA stimulation and enriched with IL-10- and TGF-β-producing NK cells. HLA-G+ NK do not show cytotoxic activity and strongly decrease both cytotoxicity and expression of perforin, granzyme B and CD107a of HLA-G- NK cells, but do not affect IFN-γ production. HLA-G neutralization antagonized the suppressive effects, leading to a 88% restoration of cytotoxic capacity of HLA-G- NK cells. In breast cancer patients, an increased number of circulating HLA-G+NK cells compared to healthy women (6.8±1.8, n=21; 4.0±1.1, n=6; p=0.001) has been detected. Obtained data suggest that increased number of suppressive HLA-G+ NK cells may be included into cohort of immunosuppressive cells mediating escape of NK-sensitive tumor cells from cytolysis.