%0 Journal Article
%A Murad, Shafiq
%A Michen, Susanne
%A Becker, Alexander
%A Füssel, Monika
%A Schackert, Gabriele
%A Tonn, Torsten
%A Momburg, Frank
%A Temme, Achim
%T NKG2C+ NK Cells for Immunotherapy of Glioblastoma Multiforme.
%J International journal of molecular sciences
%V 23
%N 10
%@ 1422-0067
%C Basel
%I Molecular Diversity Preservation International
%M DKFZ-2022-01119
%P 5857
%D 2022
%X In glioblastoma, non-classical human leucocyte antigen E (HLA-E) and HLA-G are frequently overexpressed. HLA-E loaded with peptides derived from HLA class I and from HLA-G contributes to inhibition of natural killer (NK) cells with expression of the inhibitory receptor CD94/NKG2A. We investigated whether NK cells expressing the activating CD94/NKG2C receptor counterpart were able to exert anti-glioma effects. NKG2C+ subsets were preferentially expanded by a feeder cell line engineered to express an artificial disulfide-stabilized trimeric HLA-E ligand (HLA-E*spG). NK cells expanded by a feeder cell line, which facilitates outgrowth of conventional NKG2A+, and fresh NK cells, were included for comparison. Expansion via the HLA-E*spG feeder cells selectively increased the fraction of NKG2C+ NK cells, which displayed a higher frequency of KIR2DL2/L3/S2 and CD16 when compared to expanded NKG2A+ NK cells. NKG2C+ NK cells exhibited increased cytotoxicity against K562 and KIR:HLA-matched and -mismatched primary glioblastoma multiforme (GBM) cells when compared to NKG2A+ NK cells and corresponding fresh NK cells. Cytotoxic responses of NKG2C+ NK cells were even more pronounced when utilizing target cells engineered with HLA-E*spG. These findings support the notion that NKG2C+ NK cells have potential therapeutic value for treating gliomas.
%K HLA-E (Other)
%K HLA-G (Other)
%K NK cells (Other)
%K brain cancer (Other)
%K glioblastoma (Other)
%K immunotherapy (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35628668
%R 10.3390/ijms23105857
%U https://inrepo02.dkfz.de/record/180126