Dexamethasone and lactoferrin induced PMN-MDSCs relieved inflammatory adverse events of anti-cancer therapy without tumor promotion.
Commun Biol
; 4(1): 252, 2021 02 26.
Article
em En
| MEDLINE
| ID: mdl-33637832
ABSTRACT
In this era of immune checkpoint inhibitors, inflammatory adverse events of anti-cancer therapies continue to pose a major challenge. Glucocorticoids, as the mainstay, were limited by serious side effects. Glucocorticoids induce myeloid-derived suppressor cells (MDSCs), and lactoferrin-induced polymorphonuclear MDSCs (PMN-MDSCs) were shown to relieve inflammatory conditions. Combined treatment with dexamethasone (DXM) and lactoferrin increased the generation of PMN-MDSCs in vitro (DXM/lactoferrin PMN-MDSCs) compared to DXM or lactoferrin treatment alone. DXM/lactoferrin PMN-MDSCs were distinct from tumor PMN-MDSCs in vivo with regard to gene expression profiles. DXM upregulated the myeloid cell response to lactoferrin by inducing the lactoferrin receptor Lrp1. DXM/lactoferrin PMN-MDSCs presented anti-bacterial capability, increased PGE2 production, increased survival capability, and decreased tumor tissue homing. Transfer of DXM/lactoferrin PMN-MDSCs relieved cisplatin-induced acute kidney failure, bleomycin-induced interstitial pneumonia, and allergic pneumonitis effectively without promoting tumor development. Our study shows that DXM/lactoferrin PMN-MDSCs are a promising cell therapy for inflammatory adverse events of anti-cancer therapies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pneumonia
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Dexametasona
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Doenças Pulmonares Intersticiais
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Transferência Adotiva
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Injúria Renal Aguda
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Células Supressoras Mieloides
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Lactoferrina
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Anti-Inflamatórios
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Commun Biol
Ano de publicação:
2021
Tipo de documento:
Article