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

Guang Yang; Minjie Gao; Yiwen Zhang; Yuanyuan Kong; Lu Gao; Yi Tao; Ying Han; Huiqun Wu; Xiuqin Meng; Hongwei Xu; Fenghuang Zhan; Xiaosong Wu; Jumei Shi

doi:10.18632/oncotarget.4831

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Research Papers:

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

Guang Yang, Minjie Gao, Yiwen Zhang, Yuanyuan Kong, Lu Gao, Yi Tao, Ying Han, Huiqun Wu, Xiuqin Meng, Hongwei Xu, Fenghuang Zhan, Xiaosong Wu and Jumei Shi _

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Oncotarget. 2015; 6:26982-26994. https://doi.org/10.18632/oncotarget.4831

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Abstract

Guang Yang1, Minjie Gao1, Yiwen Zhang1, Yuanyuan Kong1, Lu Gao1, Yi Tao1, Ying Han1, Huiqun Wu1, Xiuqin Meng1, Hongwei Xu2, Fenghuang Zhan2, Xiaosong Wu1, Jumei Shi1

1Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China

2Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA

Correspondence to:

Jumei Shi, e-mail: [email protected]

Xiaosong Wu, e-mail: [email protected]

Keywords: carfilzomib, multiple myeloma, natural killer cell, proteasome inhibitor, histocompatibility antigens class I

Received: April 19, 2015 Accepted: August 07, 2015 Published: August 20, 2015

ABSTRACT

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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Research Papers:

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

Abstract