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

Oncotarget
Guang YangJumei Shi

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.

References

Jul 1, 1992·The Journal of Experimental Medicine·E J BaasH L Ploegh
Jul 1, 1990·Immunology Today·H G Ljunggren, K Kärre
Aug 17, 2002·Current Opinion in Immunology·Karina L McQueen, Peter Parham
Dec 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wing LeungRupert Handgretinger
Feb 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Karine BreckpotKris Thielemans
Nov 30, 2004·Science·Eric VivierFrédéric Vély
Dec 18, 2004·Journal of Immunological Methods·Galit AlterMarcus Altfeld
Jun 17, 2005·The New England Journal of Medicine·Paul G RichardsonUNKNOWN Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators
Jul 15, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jinfu YangChristopher J Kirk
Jan 18, 2012·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·William J MurphyJeffrey S Miller
Mar 14, 2013·Blood·Gösta GahrtonUNKNOWN EBMT Chronic Malignancies Working Party Plasma Cell Disorders Subcommittee
May 23, 2013·Expert Opinion on Biological Therapy·Massimo GentileFortunato Morabito
Jul 10, 2013·Expert Opinion on Drug Metabolism & Toxicology·Chiara PautassoAntonio Palumbo
Mar 19, 2014·Seminars in Immunology·Nataliya ShifrinMichele Ardolino
Apr 5, 2014·British Journal of Haematology·Marie-Christiane VekemansAugustin Ferrant

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Citations

May 10, 2019·Expert Review of Hematology·Abdullah M KhanDon M Benson
Mar 21, 2018·Cancer Immunology, Immunotherapy : CII·Korbinian N KroppDaniela Dörfel
May 8, 2018·Journal of Leukocyte Biology·Pan LiuFuling Zhou

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Methods Mentioned

BETA
flow cytometry
Assay
fluorescence microscopy
FCS

Software Mentioned

FCS Express
SPSS

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