Hypoxia-adapted Multiple Myeloma Stem Cells Resist γδ-T-Cell-mediated Killing by Modulating the Mevalonate Pathway.
Multiple myeloma
hypoxia
isopentenyl pyrophosphate
mevalonate pathway
myeloma stem-like cells
γδ T cells
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Feb 2023
Feb 2023
Historique:
received:
13
11
2022
revised:
02
12
2022
accepted:
05
12
2022
entrez:
25
1
2023
pubmed:
26
1
2023
medline:
28
1
2023
Statut:
ppublish
Résumé
The prognosis of patients with multiple myeloma (MM) has recently improved due to the emergence of new molecular targeting agents. However, MM remains incurable because MM stem cells are resistant to these agents. Therefore, it is essential to develop strategies to eradicate MM stem cells. We have previously demonstrated that MM cells cultured under prolonged hypoxic conditions (1% O We used a combination of flow cytometry, liquid chromatography-tandem mass spectrometry, and western blotting methods to investigate the cytotoxicity of γδ T cells against MM-HA cells and measured the amounts of IPP in MM-HA cells and their supernatants. The cytotoxicity of γδ T cells against MM-HA cells was significantly lower than that against MM cells cultured under normoxic conditions (20% O The cytotoxicity of γδ T cells against MM-HA cells was suppressed by the reduced IPP accumulation by modulating the mevalonate pathway in MM-HA cells.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
The prognosis of patients with multiple myeloma (MM) has recently improved due to the emergence of new molecular targeting agents. However, MM remains incurable because MM stem cells are resistant to these agents. Therefore, it is essential to develop strategies to eradicate MM stem cells. We have previously demonstrated that MM cells cultured under prolonged hypoxic conditions (1% O
MATERIALS AND METHODS
METHODS
We used a combination of flow cytometry, liquid chromatography-tandem mass spectrometry, and western blotting methods to investigate the cytotoxicity of γδ T cells against MM-HA cells and measured the amounts of IPP in MM-HA cells and their supernatants.
RESULTS
RESULTS
The cytotoxicity of γδ T cells against MM-HA cells was significantly lower than that against MM cells cultured under normoxic conditions (20% O
CONCLUSION
CONCLUSIONS
The cytotoxicity of γδ T cells against MM-HA cells was suppressed by the reduced IPP accumulation by modulating the mevalonate pathway in MM-HA cells.
Identifiants
pubmed: 36697063
pii: 43/2/547
doi: 10.21873/anticanres.16191
doi:
Substances chimiques
Mevalonic Acid
S5UOB36OCZ
Receptors, Antigen, T-Cell, gamma-delta
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
547-555Informations de copyright
Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.