title: Carfilzomib enhances natural killer cell-mediated lysis of myeloma linked with decreasing expression of HLA class I.
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.
authors: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Guang
authors: G
authors: Yang
authors: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Minjie
authors: M
authors: Gao
authors: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Yiwen
authors: Y
authors: Zhang
authors: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Yuanyuan
authors: Y
authors: Kong
authors: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Lu
authors: L
authors: Gao
authors: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Yi
authors: Y
authors: Tao
authors: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Ying
authors: Y
authors: Han
authors: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Huiqun
authors: H
authors: Wu
authors: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Xiuqin
authors: X
authors: Meng
authors: Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA.
authors: Hongwei
authors: H
authors: Xu
authors: Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA.
authors: Fenghuang
authors: F
authors: Zhan
authors: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Xiaosong
authors: X
authors: Wu
authors: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Jumei
authors: J
authors: Shi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008024:Ligands; D008856:Microscopy, Fluorescence; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry*; D061988:Proteasome Inhibitors / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D015395:Histocompatibility Antigens Class I; D007155:Immunologic Factors; D008024:Ligands; D009842:Oligopeptides; D061988:Proteasome Inhibitors; C524865:carfilzomib
keywords: carfilzomib; histocompatibility antigens class I; multiple myeloma; natural killer cell; proteasome inhibitor