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Updated: Aug 16, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Monalizumab efficacy correlates with HLA-E surface expression and NK cell activity in head and neck squamous
Jeongjae Lee1,2, Bhumsuk Keam3,4, Ha-Ram Park1
1Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
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.
Insights
Monalizumab, an NKG2A inhibitor, shows efficacy against head and neck cancers expressing HLA-E. Enhancing NK cell activity with cytokines or cetuximab boosts monalizumab effectiveness, especially in HLA-E low tumors.
Area of Science:
- Immunology and Cancer Research
- Molecular and Cellular Biology
Background:
- NKG2A is an inhibitory receptor on NK and T cells that binds to HLA-E on cancer cells, facilitating immune evasion.
- Head and neck squamous cell carcinoma (HNSCC) can express HLA-E, potentially hindering anti-tumor immune responses.
Purpose of the Study:
- To investigate the correlation between HLA-E surface expression on HNSCC cell lines and the efficacy of monalizumab, an NKG2A inhibitor.
- To assess monalizumab's ability to restore NK cell activity against HNSCC.
Main Methods:
- HNSCC cell lines were exposed to IFN-γ to modulate HLA-E expression, measured via flow cytometry.
- NK cell-mediated cytotoxicity was evaluated using CD107a degranulation and 51Cr release assays after IL-2 and IL-15 stimulation.
- The impact of monalizumab, alone and in combination with cetuximab, was assessed on NK cell activity.
Main Results:
- HLA-E expression on HNSCC cell lines varied and increased upon IFN-γ exposure.
- Higher HLA-E expression correlated with greater inhibition of NK cell cytotoxicity, where monalizumab demonstrated high efficacy.
- Combining monalizumab with cetuximab or stimulating NK cells with cytokines enhanced monalizumab's efficacy, even in HLA-E low HNSCC.
Conclusions:
- Monalizumab's efficacy is directly related to HLA-E surface expression on HNSCC.
- Enhancing NK cell activity through combination therapies (cetuximab) or cytokine stimulation can improve monalizumab's potency.
- Monalizumab shows potential as a therapeutic agent for HLA-E-positive tumors, with improved outcomes achievable by boosting NK cell function.
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