Back to Search Start Over

Monalizumab efficacy correlates with HLA-E surface expression and NK cell activity in head and neck squamous carcinoma cell lines.

Authors :
Lee, Jeongjae
Keam, Bhumsuk
Park, Ha-Ram
Park, Ji-Eun
Kim, Soyeon
Kim, Miso
Kim, Tae Min
Kim, Dong-Wan
Heo, Dae Seog
Source :
Journal of Cancer Research & Clinical Oncology. Aug2023, Vol. 149 Issue 9, p5705-5715. 11p.
Publication Year :
2023

Abstract

Purpose: NKG2A, an inhibitory receptor expressed on NK cells and T cells, leads to immune evasion by binding to HLA-E expressed on cancer cells. Here, we investigated the relationship between HLA-E surface expression on head and neck squamous cell carcinoma (HNSCC) cell lines and the efficacy of monalizumab, an NKG2A inhibitor, in promoting NK cell activity. Methods: Six HNSCC cell lines were used as target cells. After exposure to IFN- γ, HLA-E surface expression on HNSCC cell lines was measured by flow cytometry. Peripheral blood mononuclear cells (PBMCs) from healthy donors and isolated NK cells were used as effector cells. NK cells were stimulated by treatment with IL-2 and IL-15 for 5 days, and NK cell-induced cytotoxicity was analyzed by CD107a degranulation and 51Cr release assays. Results: We confirmed that HLA-E expression was increased by IFN-γ secreted by NK cells and that HLA-E expression was different for each cell line upon exposure to IFN-γ. Cell lines with high HLA-E expression showed stronger inhibition of NK cell cytotoxicity, and efficacy of monalizumab was high. Combination with cetuximab increased the efficacy of monalizumab. In addition, stimulation of isolated NK cells with IL-2 and IL-15 increased the efficacy of monalizumab, even in the HLA-E low groups. Conclusion: Monalizumab efficacy was correlated with HLA-E surface expression and was enhanced when NK cell activity was increased by cetuximab or cytokines. These results suggest that monalizumab may be potent against HLA-E-positive tumors and that monalizumab efficacy could be improved by promoting NK cell activity. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01715216
Volume :
149
Issue :
9
Database :
Academic Search Index
Journal :
Journal of Cancer Research & Clinical Oncology
Publication Type :
Academic Journal
Accession number :
165048941
Full Text :
https://doi.org/10.1007/s00432-022-04532-x