Myeloma cells resistance to NK cell lysis mainly involves an HLA class I-dependent mechanism.
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.
Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Minjie
M
Gao
Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Lu
L
Gao
Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Guang
G
Yang
Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Yi
Y
Tao
Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Jun
J
Hou
Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA.
Hongwei
H
Xu
Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Xiaojing
X
Hu
Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Ying
Y
Han
Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Qianqiao
Q
Zhang
Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA.
Fenghuang
F
Zhan
Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China shijumei@hotmail.com wuxiaosong@gmail.com.
Xiaosong
X
Wu
Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China shijumei@hotmail.com wuxiaosong@gmail.com.
Jumei
J
Shi
D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology* / Q000473:pathology
D006680:HLA Antigens
HLA class I; cytotoxicity; myeloma; natural killer cells