期刊
PHARMACEUTICALS
卷 14, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/ph14090864
关键词
programmed cell death ligand-1; ezrin; radixin; moesin; colorectal cancer; immune checkpoint inhibitor; post-translational modification
资金
- Osaka Ohtani University Research Foundation
- Sugiura Memorial Foundation
- JSPS KAKENHI [JP20K07118]
- Kobayashi Foundation
The interaction of PD-L1 with ERM proteins in colorectal adenocarcinoma cells can affect its expression on the cell membrane, thereby potentially modulating the efficacy of PD-1/PD-L1 blockade therapies.
Programmed cell death ligand-1 (PD-L1), an immune checkpoint protein highly expressed on the cell surface in various cancer cell types, binds to programmed cell death-1 (PD-1), leading to T-cell dysfunction and tumor survival. Despite clinical successes of PD-1/PD-L1 blockade therapies, patients with colorectal cancer (CRC) receive little benefit because most cases respond poorly. Because high PD-L1 expression is associated with immune evasion and poor prognosis in CRC patients, identifying potential modulators for the plasma membrane localization of PD-L1 may represent a novel therapeutic strategy for enhancing the efficacy of PD-1/PD-L1 blockade therapies. Here, we investigated whether PD-L1 expression in human colorectal adenocarcinoma cells (LS180) is affected by ezrin/radixin/moesin (ERM), functioning as scaffold proteins that crosslink plasma membrane proteins with the actin cytoskeleton. We observed colocalization of PD-L1 with all three ERM proteins in the plasma membrane and detected interactions involving PD-L1, the three ERM proteins, and the actin cytoskeleton. Furthermore, gene silencing of ezrin and radixin, but not of moesin, substantially decreased the expression of PD-L1 on the cell surface without affecting its mRNA level. Thus, in LS180 cells, ezrin and radixin may function as scaffold proteins mediating the plasma membrane localization of PD-L1, possibly by post-translational modification.
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