期刊
JOURNAL OF CLINICAL MEDICINE
卷 11, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/jcm11092457
关键词
programmed death ligand-1; immune checkpoint molecules; ezrin; radixin; moesin; ovarian cancer; cancer immunotherapy
资金
- Osaka Ohtani University Research Foundation
- Sugiura Memorial Foundation
- Japan Society for the Promotion of Science [JSPS KAKENHI] [JP20K07118]
- Kobayashi Foundation
Programmed death ligand-1 (PD-L1) is a molecule on the plasma membrane of cancer cells that negatively regulates immune surveillance. This study suggests that ezrin may be responsible for the plasma membrane expression of PD-L1 in ovarian cancer cells, making it a potential therapeutic target for improving immune checkpoint inhibitor treatment.
Programmed death ligand-1 (PD-L1) is one of the immune checkpoint molecule localized on the plasma membrane of numerous cancer cells that negatively regulates T-cell-mediated immunosurveillance. Despite the remarkable efficacy and safety profile of immune checkpoint inhibitors (ICIs), such as anti-PD-L1 antibodies, restricted poor therapeutic responses to ICIs are often observed in patients with ovarian cancer. Because higher expression of PD-L1 in advanced ovarian cancer is associated with a decreased survival rate, identifying the potential molecules to regulate the plasma membrane expression of PD-L1 may provide a novel therapeutic strategy to improve the efficacy of ICIs against ovarian cancers. Here, we reveal the involvement of the ezrin/radixin/moesin (ERM) family, which crosslinks transmembrane proteins with the actin cytoskeleton by serving as a scaffold protein, in the plasma membrane expression of PD-L1 in the human epithelial ovarian cancer cell line A2780. Our results demonstrate that PD-L1 and all three ERMs were expressed at the mRNA and protein levels in A2780 cells, and that PD-L1 was highly colocalized with ezrin and moesin, but moderately with radixin, in the plasma membrane. Interestingly, RNA interference-mediated gene silencing of ezrin, but not of radixin or moesin, substantially reduced the plasma membrane expression of PD-L1 without altering its mRNA expression. In conclusion, our results indicate that ezrin may be responsible for the plasma membrane expression of PD-L1, possibly by serving as a scaffold protein in A2780 cells. Ezrin is a potential therapeutic target for improving the efficacy of ICIs against ovarian cancers.
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