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Monographic Report
Dual immunological regulation effects of cetuximab on multidrug resistant nasopharyngeal carcinoma CNE2/DDP cells and NK cells
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Abstract:
Objective: To investigate the effects of cetuximab on NKG2D ligands (NKG2DLs) expressions in multidrug resistant nasopharyngeal carcinoma CNE2/DDP cells and IFNγ production in NK cells. Methods: EGFR expressions on CNE2/DDP cells with high and low ABCG2 expression (ABCG2highCNE2/DDP cells and ABCG2lowCNE2/DDP cells) and NKG2DLs expressions on ABCG2high and ABCG2lowCNE2/DDP cells before and after cetuximab treatment were detected by flow cytomertry. ABCG2high and ABCG2lowCNE2/DDP cells were cocultured with NK cells before and after cetuximab treatment, and then IFNγ levels in the supernatants of different groups were detected by ELISA. Cytotoxicity of NK cells against CNE2/DDP cells was measured by LDH releasing assay in different groups. Results: EGFR expressions in ABCG2 high and ABCG2lowCNE2/DDP cells were (43.60±2.01)% and (47.20±2.07)%, respectively. The expressions of MICA, MICB, ULBP1, and ULBP2 on ABCG2hgh and ABCG2lowCNE2/DDP cells were upregulated by cetuximab stimulation, while ULBP3 expression on ABCG2highCNE2/DDP cells was downregulated by cetuximab stimulation. IFNγ levels in coculture systems were significantly increased after ABCG2low and ABCG2highCNE2/DDP cells were treated with cetuximab (P<0.01). Cetuximab enhanced cytotoxic sensitivities of ABCG2high and ABCG2lowCNE2/DDP cells in response to NK cells (P<0.01). Conclusion: Cetuximab exerts a dual immunological regulation by upregulating NKG2DLs expressions on nasopharyngeal carcinoma CNE2/DDP cells and stimulating IFNγ production by NK cells indirectly.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 30973454), and the Key Program of Natural Science Foundation of Guangdong Province (No. 9251051501000007)
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