Upregulation of HLA Class I Expression on Tumor Cells by the Anti-EGFR Antibody Nimotuzumab

摘要

FIGURE 1. Nimotuzumab-induced EGFR inhibition enhances surface expression of HLA-I antigens in human tumor cells. (A) Regulation of cell surface expression of HLA-I molecules by EGF-mediated EGFR signaling was measured by flow cytometry. Cells were cultured in 1% FCS RPMI-1640 alone or supplemented with EGF (0.08 nM) during 48 h. (B,C) HLA-ABC, HLA-A, or HLA-B surface expression was assessed by flow cytometry in EGFRI-treated cells. Cells were treated with AG1478 (5 μM), nimotuzumab or cetuximab (10 μg/ml) in 1% FCS, 0.08 nM EGF RPMI-1640 medium during 96 h. Cells cultured in the presence of human IFN-γ (800 UI/ml) during 48 h were used as control of maximum HLA-I induction. Basal HLA-I expression was determined in untreated cells. For (A–C) bars represent a mean of HLA-I Δ MFI = MFI (staining with antibodies specific for HLA-I antigens) – MFI (staining with isotype control) values ± SD of three-four independent experiments. For (B), a media of HLA-ABC increase index = HLA-ABC ΔMFI (treated-cells)/HLA-ABC ΔMFI (untreated-cells) values is included for each experimental group. For (A), statistical analyses were performed using Mann–Whitney U-test (?P < 0.05). For (B,C), analyses were performed according to Kruskal–Wallis test and Dunn post-test (different letters indicate statistical differences).