Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 415, Issue 1, Pages 187-192Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2011.10.057
Keywords
Myeloma; Natural killer cell; Proteasome inhibitor; Lactacystin
Categories
Funding
- National Natural Science Foundation of China [81071856, 30973450]
- Shanghai Pujiang Program [11PJ1407900]
- Shanghai Tenth People's Hospital [10RD103, 11SC103]
Ask authors/readers for more resources
Modulation of inhibitory and activating natural killer (NK) receptor ligands on tumor cells represents a promising therapeutic approach against cancer, including multiple myeloma (MM). Human leukocyte antigen (HLA) class I molecules, the NK cell inhibitory killer cell immunoglobulin-like receptor (KIR) ligands, are critical determinants of NK cell activity. Proteasome inhibitors have demonstrated significant anti-myeloma activity in MM patients. In this study, we evaluated the effect of proteasome inhibitors on the surface expression of class I in human MM cells. We found that proteasome inhibitors downregulated surface expression of class I in a dose- and time-dependent manner in MM cell line and patient MM cells. No significant changes in the expression of the MHC class I chain-related molecules (MIC) A/B and the UL16-binding proteins (ULBPs) 1-3 were observed. Downregulation of class I by lactacystin (LAC) significantly enhances NK cell-mediated lysis of MM. Furthermore, the downregulation degree of class I was associated with increased susceptibility of myeloma cells to NK cell killing. HLA blocking antibody produced results that were similar to the findings from proteasome inhibitor. Taken together, our data suggest that proteasome inhibitors, possible targeting inhibitory KIR ligand class I on tumor cells, may contribute to the activation of cytolytic effector NK cells in vitro, enhancing their anti-myeloma activity. Our findings provide a rationale for clinical evaluation of proteasome inhibitor, alone or in combination, as a novel approach to immunotherapy of MM. (C) 2011 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available