PMID- 26323098
OWN - NLM
STAT- MEDLINE
DCOM- 20160815
LR  - 20220331
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 29
DP  - 2015 Sep 29
TI  - Carfilzomib enhances natural killer cell-mediated lysis of myeloma linked with 
      decreasing expression of HLA class I.
PG  - 26982-94
LID - 10.18632/oncotarget.4831 [doi]
AB  - 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.
FAU - Yang, Guang
AU  - Yang G
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Gao, Minjie
AU  - Gao M
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Zhang, Yiwen
AU  - Zhang Y
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Kong, Yuanyuan
AU  - Kong Y
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Gao, Lu
AU  - Gao L
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Tao, Yi
AU  - Tao Y
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Han, Ying
AU  - Han Y
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Wu, Huiqun
AU  - Wu H
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Meng, Xiuqin
AU  - Meng X
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Xu, Hongwei
AU  - Xu H
AD  - Department of Internal Medicine, University of Iowa, Carver College of Medicine, 
      Iowa City, Iowa, USA.
FAU - Zhan, Fenghuang
AU  - Zhan F
AD  - Department of Internal Medicine, University of Iowa, Carver College of Medicine, 
      Iowa City, Iowa, USA.
FAU - Wu, Xiaosong
AU  - Wu X
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Shi, Jumei
AU  - Shi J
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Immunologic Factors)
RN  - 0 (Ligands)
RN  - 0 (Oligopeptides)
RN  - 0 (Proteasome Inhibitors)
RN  - 72X6E3J5AR (carfilzomib)
SB  - IM
MH  - Antineoplastic Agents/chemistry
MH  - Cell Line, Tumor
MH  - Cytotoxicity, Immunologic/drug effects/immunology
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation
MH  - Flow Cytometry
MH  - Histocompatibility Antigens Class I/*metabolism
MH  - Humans
MH  - Immunologic Factors/chemistry
MH  - K562 Cells
MH  - Killer Cells, Natural/drug effects/*immunology
MH  - Ligands
MH  - Microscopy, Fluorescence
MH  - Multiple Myeloma/*drug therapy/*immunology/metabolism
MH  - Oligopeptides/*chemistry
MH  - Proteasome Inhibitors/chemistry
PMC - PMC4694968
OTO - NOTNLM
OT  - carfilzomib
OT  - histocompatibility antigens class I
OT  - multiple myeloma
OT  - natural killer cell
OT  - proteasome inhibitor
COIS- CONFLICTS OF INTERESTS The authors disclose no potential conflicts of interest.
EDAT- 2015/09/01 06:00
MHDA- 2016/08/16 06:00
PMCR- 2015/09/29
CRDT- 2015/09/01 06:00
PHST- 2015/04/19 00:00 [received]
PHST- 2015/08/07 00:00 [accepted]
PHST- 2015/09/01 06:00 [entrez]
PHST- 2015/09/01 06:00 [pubmed]
PHST- 2016/08/16 06:00 [medline]
PHST- 2015/09/29 00:00 [pmc-release]
AID - 4831 [pii]
AID - 10.18632/oncotarget.4831 [doi]
PST - ppublish
SO  - Oncotarget. 2015 Sep 29;6(29):26982-94. doi: 10.18632/oncotarget.4831.