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001     180126
005     20240229145607.0
024 7 _ |a 10.3390/ijms23105857
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024 7 _ |a 1422-0067
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037 _ _ |a DKFZ-2022-01119
041 _ _ |a English
082 _ _ |a 540
100 1 _ |a Murad, Shafiq
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245 _ _ |a NKG2C+ NK Cells for Immunotherapy of Glioblastoma Multiforme.
260 _ _ |a Basel
|c 2022
|b Molecular Diversity Preservation International
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520 _ _ |a 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.
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650 _ 7 |a HLA-E
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650 _ 7 |a HLA-G
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650 _ 7 |a NK cells
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650 _ 7 |a brain cancer
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650 _ 7 |a glioblastoma
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650 _ 7 |a immunotherapy
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700 1 _ |a Michen, Susanne
|0 0000-0002-5726-386X
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700 1 _ |a Becker, Alexander
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700 1 _ |a Füssel, Monika
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700 1 _ |a Schackert, Gabriele
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700 1 _ |a Tonn, Torsten
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700 1 _ |a Momburg, Frank
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700 1 _ |a Temme, Achim
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773 _ _ |a 10.3390/ijms23105857
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