Myricetin inhibits interferon-γ-induced PD-L1 and IDO1 expression in lung cancer cells.
Biochem Pharmacol
; 197: 114940, 2022 03.
Article
em En
| MEDLINE
| ID: mdl-35120895
ABSTRACT
Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints induced by interferon-γ (IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. In this study, MY was identified to inhibit IFN-γ-induced PD-L1 expression in human lung cancer cells. It also reduced the expression of IDO1 and the production of kynurenine which is the product catalyzed by IDO1, while didn't show obvious effect on the expression of major histocompatibility complex-I (MHC-I), a crucial molecule for antigen presentation. In addition, the function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line overexpressing PD-1. MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. Together, our research revealed a new mechanism of MY mediated anti-tumor activity and highlighted the potential implications of MY in tumor immunotherapy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Flavonoides
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Regulação Neoplásica da Expressão Gênica
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Interferon gama
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Indolamina-Pirrol 2,3,-Dioxigenase
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Antígeno B7-H1
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Neoplasias Pulmonares
Limite:
Humans
Idioma:
En
Revista:
Biochem Pharmacol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China