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  Myricetin inhibits interferon-gamma-induced PD-L1 and IDO1 expression in lung cancer cells

Chen, Y.-C., He, X.-L., Qi, L., Shi, W., Yuan, L.-W., Huang, M.-Y., et al. (2022). Myricetin inhibits interferon-gamma-induced PD-L1 and IDO1 expression in lung cancer cells. BIOCHEMICAL PHARMACOLOGY, 197: 114940. doi:10.1016/j.bcp.2022.114940.

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 Creators:
Chen, Yu-Chi, Author
He, Xin-Ling, Author
Qi, Lu, Author
Shi, Wei, Author
Yuan, Luo-Wei, Author
Huang, Mu-Yang, Author
Xu, Yu-Lian, Author
Chen, Xiuping, Author
Gu, Lei1, Author              
Zhang, Le-Le, Author
Lu, Jin-Jian, Author
Affiliations:
1Epigenetics, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_3327072              

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 Abstract: Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints induced by interferon-gamma (IFN-gamma) 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-gamma-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-gamma-treated lung cancer cells. Mechanistically, IFN-gamma 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.

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 Dates: 2022-02-012022-03
 Publication Status: Published in print
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 Identifiers: ISI: 000772629700002
DOI: 10.1016/j.bcp.2022.114940
PMID: 35120895
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Title: BIOCHEMICAL PHARMACOLOGY
Source Genre: Journal
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Pages: - Volume / Issue: 197 Sequence Number: 114940 Start / End Page: - Identifier: ISSN: 0006-2952