Proteome Analysis of Human Natural Killer Cell Derived Extracellular Vesicles for Identification of Anticancer Effectors

Cancer immunotherapy is a clinically validated therapeutic modality for cancer and has been rapidly advancing in recent years. Adoptive transfer of immune cells such as T cells and natural killer (NK) cells has emerged as a viable method of controlling the immune system against cancer. Recent eviden...

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Main Authors: Jung-Won Choi, Soyeon Lim, Jung Hwa Kang, Sung Hwan Hwang, Ki-Chul Hwang, Sang Woo Kim, Seahyoung Lee
Format: Article
Language:English
Published: MDPI AG 2020-11-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/25/21/5216
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author Jung-Won Choi
Soyeon Lim
Jung Hwa Kang
Sung Hwan Hwang
Ki-Chul Hwang
Sang Woo Kim
Seahyoung Lee
author_facet Jung-Won Choi
Soyeon Lim
Jung Hwa Kang
Sung Hwan Hwang
Ki-Chul Hwang
Sang Woo Kim
Seahyoung Lee
author_sort Jung-Won Choi
collection DOAJ
description Cancer immunotherapy is a clinically validated therapeutic modality for cancer and has been rapidly advancing in recent years. Adoptive transfer of immune cells such as T cells and natural killer (NK) cells has emerged as a viable method of controlling the immune system against cancer. Recent evidence indicates that even immune-cell-released vesicles such as NK-cell-derived exosomes also exert anticancer effect. Nevertheless, the underlying mechanisms remain elusive. In the present study, the anticancer potential of isolated extracellular vesicles (EVs) from expanded and activated NK-cell-enriched lymphocytes (NKLs) prepared by house-developed protocol was evaluated both in vitro and in vivo. Moreover, isolated EVs were characterized by using two-dimensional electrophoresis (2-DE)-based proteome and network analysis, and functional study using identified factors was performed. Our data indicated that the EVs from expanded and active NKLs had anticancer properties, and a number of molecules, such as Fas ligand, TRAIL, NKG2D, β-actin, and fibrinogen, were identified as effector candidates based on the proteome analysis and functional study. The results of the present study suggest the possibility of NK-cell-derived EVs as a viable immunotherapeutic strategy for cancer.
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spelling doaj.art-cda944b4e12047688b8e236275c9e4e32023-11-20T20:20:02ZengMDPI AGMolecules1420-30492020-11-012521521610.3390/molecules25215216Proteome Analysis of Human Natural Killer Cell Derived Extracellular Vesicles for Identification of Anticancer EffectorsJung-Won Choi0Soyeon Lim1Jung Hwa Kang2Sung Hwan Hwang3Ki-Chul Hwang4Sang Woo Kim5Seahyoung Lee6Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 210-701, KoreaInstitute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 210-701, KoreaIMMUNISBIO Co. Ltd., B2F MTP Mall, International St. Mary’s Hospital, Incheon Metropolitan City 22711, KoreaIMMUNISBIO Co. Ltd., B2F MTP Mall, International St. Mary’s Hospital, Incheon Metropolitan City 22711, KoreaInstitute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 210-701, KoreaInstitute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 210-701, KoreaInstitute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 210-701, KoreaCancer immunotherapy is a clinically validated therapeutic modality for cancer and has been rapidly advancing in recent years. Adoptive transfer of immune cells such as T cells and natural killer (NK) cells has emerged as a viable method of controlling the immune system against cancer. Recent evidence indicates that even immune-cell-released vesicles such as NK-cell-derived exosomes also exert anticancer effect. Nevertheless, the underlying mechanisms remain elusive. In the present study, the anticancer potential of isolated extracellular vesicles (EVs) from expanded and activated NK-cell-enriched lymphocytes (NKLs) prepared by house-developed protocol was evaluated both in vitro and in vivo. Moreover, isolated EVs were characterized by using two-dimensional electrophoresis (2-DE)-based proteome and network analysis, and functional study using identified factors was performed. Our data indicated that the EVs from expanded and active NKLs had anticancer properties, and a number of molecules, such as Fas ligand, TRAIL, NKG2D, β-actin, and fibrinogen, were identified as effector candidates based on the proteome analysis and functional study. The results of the present study suggest the possibility of NK-cell-derived EVs as a viable immunotherapeutic strategy for cancer.https://www.mdpi.com/1420-3049/25/21/5216extracellular vesiclesnatural-killer-enriched lymphocytes (NKL)anticancer immunotherapyproteome analysis
spellingShingle Jung-Won Choi
Soyeon Lim
Jung Hwa Kang
Sung Hwan Hwang
Ki-Chul Hwang
Sang Woo Kim
Seahyoung Lee
Proteome Analysis of Human Natural Killer Cell Derived Extracellular Vesicles for Identification of Anticancer Effectors
Molecules
extracellular vesicles
natural-killer-enriched lymphocytes (NKL)
anticancer immunotherapy
proteome analysis
title Proteome Analysis of Human Natural Killer Cell Derived Extracellular Vesicles for Identification of Anticancer Effectors
title_full Proteome Analysis of Human Natural Killer Cell Derived Extracellular Vesicles for Identification of Anticancer Effectors
title_fullStr Proteome Analysis of Human Natural Killer Cell Derived Extracellular Vesicles for Identification of Anticancer Effectors
title_full_unstemmed Proteome Analysis of Human Natural Killer Cell Derived Extracellular Vesicles for Identification of Anticancer Effectors
title_short Proteome Analysis of Human Natural Killer Cell Derived Extracellular Vesicles for Identification of Anticancer Effectors
title_sort proteome analysis of human natural killer cell derived extracellular vesicles for identification of anticancer effectors
topic extracellular vesicles
natural-killer-enriched lymphocytes (NKL)
anticancer immunotherapy
proteome analysis
url https://www.mdpi.com/1420-3049/25/21/5216
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