NKG2C+ NK Cells for Immunotherapy of Glioblastoma Multiforme

International Journal of Molecular Sciences

Frank Momburg¹  Monika Füssel²  Alexander Becker³  Susanne Michen³  Shafiq Murad³  Gabriele Schackert³  Achim Temme³  Torsten Tonn⁴ 

[1] Antigen Presentation and T/NK Cell Activation Group (D121), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany;DKMS Life Science Lab GmbH, St. Petersburger Str. 2, 01069 Dresden, Germany;Department of Neurosurgery, Section Experimental Neurosurgery/Tumor Immunology, University Hospital Carl Gustav Carus, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany;Department of Transfusion Medicine, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany;

关键词: brain cancer;    glioblastoma;    HLA-E;    HLA-G;    NK cells;    immunotherapy;   

DOI  :  10.3390/ijms23105857

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown