Modulation of Immune Checkpoint Molecule PD-L1 Expression via Scaffold Proteins in the Ovarian Clear Cell Carcinoma Common in Japanese Women

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  • Kobori Takuro
    Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University Laboratory of Pathophysiology and Pharmacotherapeutics, Faculty of Pharmacy, Osaka Ohtani University
  • Ito Yui
    Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University
  • Urashima Yoko
    Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University
  • Ito Takuya
    Laboratory of Natural Medicines, Faculty of Pharmacy, Osaka Ohtani University
  • Obata Tokio
    Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University

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  • 日本人女性に多い卵巣明細胞腺癌における足場タンパク質を介した免疫チェックポイント分子PD-L1の発現調節

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<p> The morbidity and mortality in ovarian cancer has been increasing yearly in Japan and those are dramatically increasingly among Adolescent and Young Adult (AYA). Ovarian clear cell carcinoma (OCCC) is a specific pathological type of ovarian cancer that has an extremely high incidence rate in Japan and is resistant to conventional chemotherapy, leading to an extremely poor prognosis. Although immune checkpoint blockade therapy targeting the Programmed death-1 (PD-1) /PD-ligand 1 (PD-L1) axis have emerged as promising treatments for OCCC, a small subset of patients derives clinical benefit from this therapy. Thus, further exploration of novel therapeutic targets to block the PD-1/PD-L1 axis is warranted.</p><p> Ezrin/Radixin/Moesin (ERM) crosslink several cell surface cancer-related proteins and intracellular actin cytoskeleton as scaffold proteins, contributing to their cell surface localization. Here, we determined role of ERM in the cell surface localization of PD-L1 in OVTOKO cell, derived from a Japanese patient with OCCC. Immunofluorescence and immunoprecipitation analysis suggests that in OVTOKO cell PD-L1 colocalized and interacted with all three ERM in the plasma membrane. Interestingly, gene silencing of Moesin but not others significantly decreased the cell surface PD-L1 expression. In conclusion, Moesin may act as a scaffold protein for PD-L1, contributing to its cell surface localization in OVTOKO cell.</p>

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