Ezrin and Radixin Differentially Modulate Cell Surface Expression of Programmed Death Ligand-1 in Human Pancreatic Ductal Adenocarcinoma KP-2 Cells

被引:9
作者
Kobori, Takuro [1 ]
Doukuni, Rina [1 ]
Ishikawa, Honami [1 ]
Ito, Yui [1 ]
Okada, Rie [1 ]
Tanaka, Chihiro [1 ]
Tameishi, Mayuka [1 ]
Urashima, Yoko [1 ]
Ito, Takuya [2 ]
Obata, Tokio [1 ]
机构
[1] Osaka Ohtani Univ, Fac Pharm, Lab Clin Pharmaceut, Tondabayashi, Osaka 5848540, Japan
[2] Osaka Ohtani Univ, Fac Pharm, Lab Nat Med, Tondabayashi, Osaka 5848540, Japan
来源
IMMUNO | 2022年 / 2卷 / 01期
关键词
programmed death ligand-1; ezrin; radixin; moesin; pancreatic ductal adenocarcinoma; immune checkpoint blockade; P-GLYCOPROTEIN FUNCTION; CANCER; PD-L1; TRANSPORTERS; KNOCKDOWN; PROTEINS; MOESIN; LIVER; CMTM6;
D O I
10.3390/immuno2010006
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Immune checkpoint blockade (ICB) therapies, such as immune checkpoint inhibitors against programmed death ligand-1 (PD-L1), have not been successful in treating patients with pancreatic ductal adenocarcinoma (PDAC). Despite the critical role of PD-L1 in various types of cancers, the regulatory mechanism of PD-L1 expression on the cell surface of PDAC is poorly understood. Therefore, uncovering potential modulators of cell surface localisation of PD-L1 may provide a new strategy to improve ICB therapy in patients with PDAC. Here, we examined the role of ezrin/radixin/moesin (ERM) family scaffold proteins that crosslink transmembrane proteins with the actin cytoskeleton in the surface localisation of PD-L1 in KP-2 cells, a human PDAC cell line. Our results demonstrated the abundant protein expression of PD-L1, ezrin, and radixin, but not moesin, as well as their colocalisation in the plasma membrane. Interestingly, immunoprecipitation analysis detected the molecular interaction of PD-L1 with ezrin and radixin. Moreover, gene silencing of ezrin moderately decreased the mRNA and cell surface expression of PD-L1, while that of radixin greatly decreased the surface expression of PD-L1 without altering the mRNA levels. Thus, radixin and ezrin differentially modulate the cell surface localisation of PD-L1 in KP-2 cells, highlighting a potential therapeutic target to improve the current ICB therapy in PDAC.
引用
收藏
页码:68 / 84
页数:17
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