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

2015; Impact Journals LLC; Volume: 6; Issue: 29 Linguagem: Inglês

10.18632/oncotarget.4831

1949-2553

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

T-cell and B-cell Immunology

// Guang Yang 1 , Minjie Gao 1 , Yiwen Zhang 1 , Yuanyuan Kong 1 , Lu Gao 1 , Yi Tao 1 , Ying Han 1 , Huiqun Wu 1 , Xiuqin Meng 1 , Hongwei Xu 2 , Fenghuang Zhan 2 , Xiaosong Wu 1 , Jumei Shi 1 1 Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China 2 Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA Correspondence to: Jumei Shi, e-mail: shijumei@hotmail.com Xiaosong Wu, e-mail: wux163@163.com 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.