PMID- 24850305 OWN - NLM STAT- MEDLINE DCOM- 20150914 LR - 20140627 IS - 1745-7270 (Electronic) IS - 1672-9145 (Linking) VI - 46 IP - 7 DP - 2014 Jul TI - Myeloma cells resistance to NK cell lysis mainly involves an HLA class I-dependent mechanism. PG - 597-604 LID - 10.1093/abbs/gmu041 [doi] AB - 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. CI - (c) The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. FAU - Gao, Minjie AU - Gao M AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. FAU - Gao, Lu AU - Gao L AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. FAU - Yang, Guang AU - Yang G AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. FAU - Tao, Yi AU - Tao Y AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. FAU - Hou, Jun AU - Hou J AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. FAU - Xu, Hongwei AU - Xu H AD - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA. FAU - Hu, Xiaojing AU - Hu X AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. FAU - Han, Ying AU - Han Y AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. FAU - Zhang, Qianqiao AU - Zhang Q AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. FAU - Zhan, Fenghuang AU - Zhan F AD - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA. FAU - Wu, Xiaosong AU - Wu X AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China shijumei@hotmail.com wuxiaosong@gmail.com. FAU - Shi, Jumei AU - Shi J AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China shijumei@hotmail.com wuxiaosong@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140521 PL - China TA - Acta Biochim Biophys Sin (Shanghai) JT - Acta biochimica et biophysica Sinica JID - 101206716 RN - 0 (HLA Antigens) SB - IM MH - Cell Line, Tumor MH - Cytotoxicity, Immunologic MH - Down-Regulation MH - Flow Cytometry MH - Gene Expression Profiling MH - HLA Antigens/*immunology MH - Humans MH - Killer Cells, Natural/*immunology MH - Multiple Myeloma/genetics/*immunology/pathology OTO - NOTNLM OT - HLA class I OT - cytotoxicity OT - myeloma OT - natural killer cells EDAT- 2014/05/23 06:00 MHDA- 2015/09/15 06:00 CRDT- 2014/05/23 06:00 PHST- 2014/05/23 06:00 [entrez] PHST- 2014/05/23 06:00 [pubmed] PHST- 2015/09/15 06:00 [medline] AID - gmu041 [pii] AID - 10.1093/abbs/gmu041 [doi] PST - ppublish SO - Acta Biochim Biophys Sin (Shanghai). 2014 Jul;46(7):597-604. doi: 10.1093/abbs/gmu041. Epub 2014 May 21.