TY  - JOUR
AU  - Murad, Shafiq
AU  - Michen, Susanne
AU  - Becker, Alexander
AU  - Füssel, Monika
AU  - Schackert, Gabriele
AU  - Tonn, Torsten
AU  - Momburg, Frank
AU  - Temme, Achim
TI  - NKG2C+ NK Cells for Immunotherapy of Glioblastoma Multiforme.
JO  - International journal of molecular sciences
VL  - 23
IS  - 10
SN  - 1422-0067
CY  - Basel
PB  - Molecular Diversity Preservation International
M1  - DKFZ-2022-01119
SP  - 5857
PY  - 2022
AB  - 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.
KW  - HLA-E (Other)
KW  - HLA-G (Other)
KW  - NK cells (Other)
KW  - brain cancer (Other)
KW  - glioblastoma (Other)
KW  - immunotherapy (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:35628668
DO  - DOI:10.3390/ijms23105857
UR  - https://inrepo02.dkfz.de/record/180126
ER  -