|
Vol 46 No. 7: 597-607 |
[PDF] [Full Text] |
|
Myeloma cells resistance to NK cell lysis mainly involves an HLA class I-dependent mechanism |
|
Minjie Gao1,†,
Lu Gao1,†,
Guang Yang1,
Yi Tao1,
Jun Hou1,
Hongwei Xu2,
Xiaojing Hu1,
Ying Han1,
Qianqiao Zhang1,
Fenghuang Zhan2,
Xiaosong Wu1,* and
Jumei Shi1,*
|
1Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
2Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
†These authors contributed equally to this work.
|
|
Abstract 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 myeloma cells. Interestingly, no or low HLA-G surface expression was detected, although multiple HLA-G transcripts were detected in these myeloma 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 HLA class I-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.
|
|
Keywords myeloma; natural killer cells; cytotoxicity; HLA class I
|
|
Received 2014-4-8
Accepted 2014-4-23
|
|
Funding This work was supported by the grants from the National Natural Science Foundation of China (81372391, 81071856, 81228016, and 81000199), Shanghai Science and Technology Program (12410705100), and Shanghai Tenth People’s Hospital Funds (040113015).
|
|
* Correspondence address Tel: +86-21-66306764; Fax: +86-21-66301051; E-mail: [email protected] (J.S.). Tel: +86-21-66306764; Fax: +86-21-66301051; E-mail: [email protected] (X.W.)
|
|
Browse:1112 |
|