Myeloma cells resistance to NK cell lysis mainly involves an HLA class I-dependent mechanism

• Published in: Acta biochimica et biophysica Sinica Vol. 46; no. 7; pp. 597 - 604
• Main Authors: Gao, Minjie, Gao, Lu, Yang, Guang, Tao, Yi, Hou, Jun, Xu, Hongwei, Hu, Xiaojing, Han, Ying, Zhang, Qianqiao, Zhan, Fenghuang, Wu, Xiaosong, Shi, Jumei
• Format: Journal Article
• Language: English
• Published: China 01.07.2014
• Subjects: Cell Line, Tumor; Cytotoxicity, Immunologic; Down-Regulation; Flow Cytometry; Gene Expression Profiling; HLA Antigens - immunology; HLA-G; Humans; Killer Cells, Natural - immunology; Multiple Myeloma - genetics; Multiple Myeloma - immunology; Multiple Myeloma - pathology; NK细胞活性; 人类白细胞抗原; 依赖性; 分子机制; 流式细胞仪分析; 细胞裂解; 骨髓瘤细胞; HLA class I; natural killer cells; myeloma; cytotoxicity
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1093/abbs/gmu041

The anti-multiple myeloma （MM） potential of natural killer （NK） cells has been of rising interest in recent years. However, the molecular mechanism of NK cell cytotoxicity to myeloma cells remains unclear. In the present study, we investigated the expressions of human leukocyte antigen （HLA） class I and HLA-G in patient myeloma cells, and determined their relevance in patient tumor-cell susceptibility to NK cell cytotoxicity. Our results showed that patient myeloma cells （n = 12） were relatively resistant to NK-92 cell lysis, compared with myeloma cell lines （n = 7, P 〈 0.01）. Gene expression profiling and flow cytometry analysis showed that both mRNA and protein of HLA class I were highly expressed in 12 patient mycloma cells. Interestingly, no or low HLA-G surface expression was detected, although multiple HLA-G transcripts were detected in these mycloma cells. NK cell function assay showed that down-regulating HLA class I expression on patient cells by acid treatment significantly increased the susceptibility of MM cells to NK-mediated lysis. Furthermore, we found that the blocking of membrane-bound HLA class I rather than HLA-G using antibodies on myeloma samples markedly increased their susceptibility to NK-mediated killing. These results demonstrated that the resistance of patient MM cells to NK lysis mainly involves an I-ILA class l- dependent mechanism, suggesting that HLA class I may be involved in protecting MM cells from NK-mediated attack and contribute to their immune escape in vivo.