Role of Ezrin/Radixin/Moesin in the Cell Surface Localization of Immune Checkpoint Molecule PD-L1 in Human Endometrial Carcinoma Cell Line.

Kobori Takuro, Tanaka Chihiro, Ito Yui, Urashima Yoko, Ito Takuya, Takagaki Nobumasa, Obata Tokio

doi:10.34598/ayaoncology.3.1_2

<p> Immune checkpoint blockade therapy that targets immune checkpoint molecules, such as programmed death-1 (PD-1) receptor and its ligand programmed death ligand-1 (PD-L1) of the PD-1/PD-L1 pathway, has been used for the treatment of a broad spectrum of cancers. However, patients with endometrial carcinoma receive limited clinical benefits from immune checkpoint blockade therapy because of poor response rates. Therefore, novel therapeutic strategies are needed for blocking the PD-1/PD-L1 pathway in these patients. Here, we investigated the role of ezrin/radixin/moesin (ERM) family proteins in the localization of PD-L1 to the plasma membrane in HEC-265 cells, derived from a Japanese patient with endometrial carcinoma ; these proteins serve scaffolding functions for several transmembrane proteins implicated in cancers by anchoring them to the actin cytoskeleton. Immunofluorescence analysis showed that PD-L1 and all three ERM proteins preferentially localized in the plasma membrane and that PD-L1 colocalized with all three ERM proteins in the plasma membrane. Intriguingly, RNA interference-mediated knockdown of ezrin and radixin but not moesin expression disrupted the localization of PD-L1 to the cell surface. In conclusion, ezrin and radixin may equally serve as scaffold proteins primarily responsible for the plasma membrane localization of PD-L1 in HEC-265 cells.</p>

Role of Ezrin/Radixin/Moesin in the Cell Surface Localization of Immune Checkpoint Molecule PD-L1 in Human Endometrial Carcinoma Cell Line.

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