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Carfilzomib enhances natural killer cell-mediated lysis of myeloma linked with decreasing expression of HLA class I.

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Published:25th Mar 2020
Author: Yang G, Gao M, Zhang Y, Kong Y, Gao L, Tao Y et al.
Source: OncoTargets
Ref.:Oncotarget. 2015 Sep 29;6(29):26982-94.
DOI:10.18632/oncotarget.4831.

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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