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Low expression of MHC class I-related chain A and B reduces NK cell-mediated lysis in nasopharyngeal carcinoma drug-resistant cell line CNE2/DDP
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Abstract:
Objective: To analyze the expression of HLA class Ⅰ molecules and MHC classⅠ related chain A and B (MICA/MICB) in human nasopharyngeal carcinoma cell line (CNE2) and multi-drug resistant nasopharyngeal carcinoma cell line (CNE2/ DDP), and to assess their influence on NK cell-mediated lysis.Methods: Expression of HLA classⅠ molecules and MICA/MICB on the surface of CNE2 and CNE2/DDP cell lines was analyzed by flow cytometry. Cytotoxicity of NK cells (isolated from 3 healthy persons) against CNE2 and CNE2/DDP cells were detected by LDH releasing assay at different effect-to-target cell ratios (E∶T). In blocking experiments, anti-MHC class Ⅰ monoclonal antibody (mAb) (W6/32, a pan anti-HLA class Ⅰ antibody) and anti-MHC class I chain related molecules mAb (BAMO-1, specificly against MICA and MICB) were added to the target cells at a E∶T ratio of 10∶1. Results:It was found that the expression of HLA class Ⅰ molecules and MICA/MICB on CNE2 was higher than that on CNE2/DDP(Ｐ<0.01). Cytotoxicity of NK cells against CNE2 and CNE2/DDP cells was (9.37±2.14) %, (4.37±0.63 )% at E∶T ratio of 5∶1, (27.14±1.82)%, (15.79±2.87)% at E∶T ratio of 10∶1, (36.40±4.28)%, (26.20±4.18)% at E∶T ratio of 20∶1, and (54.67±2.80)%, (40.29±2.73)% at E∶T ratio of 30∶1, respectively. NK cells displayed higher cytotoxicity against parental CNE2 cells than multi-drug resistant CNE2/DDP cells(P<0.01). Expression of HLA classⅠ molecules and MICA/MICB on CNE2, CNE2/DDP cells was correlated with NK cell-mediated lysis. Blocking experiments confirmed that the killing of CNE2, CNE2/DDP cells was efficiently inhibited by BAMO-1, whereas efficiently increased by W6/32. Conclusion: Low expression of MICA/MICB in multi-drug resistant tumor cell lines leads to reduction of their susceptibility to NK lysis.
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