期刊
BIOCHEMICAL PHARMACOLOGY
卷 197, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2022.114940
关键词
Programmed death ligand-1; Myricetin; Interferon-gamma; Lung cancer; Indoleamine 2, 3-dioxygenase 1
资金
- Science and Technology Development Fund, Macau SAR [0129/2019/A3, 176/2017/A3]
- University of Macau [MYRG2018-00165-ICMS]
- Guangdong Provincial Science and Technology Innovation Strategy Special Fund (Guangdong-Hong Kong-Macau Joint Lab) [2020B1212030006]
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
- Cardio-Pulmonary Institute (CPI) [390649896]
- [EXC 2026]
In this study, it was found that myricetin (MY) can inhibit the expression of PD-L1 and IDO1 induced by interferon-gamma (IFN-gamma) in lung cancer cells and restore the function of T cells. This discovery highlights the potential role of MY in tumor immunotherapy.
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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