NKG2C+ NK Cells for Immunotherapy of Glioblastoma Multiforme
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
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.
Details
Original language | English |
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Article number | 5857 |
Journal | International journal of molecular sciences |
Volume | 23 |
Issue number | 10 |
Publication status | Published - 1 May 2022 |
Peer-reviewed | Yes |
External IDs
PubMed | 35628668 |
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ORCID | /0000-0002-5726-386X/work/142249120 |
Keywords
Sustainable Development Goals
ASJC Scopus subject areas
Keywords
- brain cancer, glioblastoma, HLA-E, HLA-G, immunotherapy, NK cells