Journal
ONCOTARGET
Volume 6, Issue 29, Pages 26982-26994Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4831
Keywords
carfilzomib; multiple myeloma; natural killer cell; proteasome inhibitor; histocompatibility antigens class I
Categories
Funding
- National Natural Science Foundation of China [81372391, 81071856, 81300443]
- Shanghai Tenth People's Hospital Funds [040113015]
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Natural killer (NK) cell-based treatments are promising therapies for multiple myeloma (MM). Carfilzomib (CFZ), is a second-generation proteasome inhibitor, used to treat relapsed and refractory MM. In this study, we determined that CFZ treatment enhanced the sensitivity of MM cells to NK cell-mediated lysis. Here, we report that CFZ decreased the expression of human leukocyte antigen (HLA) class I in a time- and dose- dependent manner. CFZ also down-regulated the expression of newly formed HLA class I on MM cells. Treatment of MM with CFZ enhanced NK cell degranulation and significantly sensitized patients' MM cells to NK cell-mediated lysis. Furthermore, the enhancement of NK cell-mediated lysis was linked with the decreased expression of HLA class I. Our findings show a novel activity of CFZ as an immunomodulating agent and suggest a possible approach to therapeutically augment NK cell function in MM patients.
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