他汀类药物通过抑制 AKT 和 β-连环蛋白信号通路降低程序性死亡配体 1（PD-L1）。

Statins Decrease Programmed Death-Ligand 1 (PD-L1) by Inhibiting AKT and β-Catenin Signaling.

机构信息

Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, Chungju 27478, Korea.

Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju 27478, Korea.

出版信息

Cells. 2021 Sep 20;10(9):2488. doi: 10.3390/cells10092488.

Retrospective observational studies have reported that statins improve clinical outcomes in patients previously treated with programmed cell death protein 1 (PD-1)-targeting monoclonal antibodies for malignant pleural mesothelioma (MPM) and advanced non-small cell lung cancer (NSCLC). In multiple mouse cancer models, de novo synthesis of mevalonate and cholesterol inhibitors was found to synergize with anti-PD-1 antibody therapy. In the present study, we investigated whether statins affect programmed death-ligand 1 (PD-L1) expression in cancer cells. Four statins, namely simvastatin, atorvastatin, lovastatin, and fluvastatin, decreased PD-L1 expression in melanoma and lung cancer cells. In addition, we found that AKT and β-catenin signaling involved PD-L1 suppression by statins. Our cellular and molecular studies provide inspiring evidence for extending the clinical evaluation of statins for use in combination with immune checkpoint inhibitor-based cancer therapy.

回顾性观察研究报告称，他汀类药物可改善先前接受程序性死亡蛋白 1（PD-1）靶向单克隆抗体治疗恶性胸膜间皮瘤（MPM）和晚期非小细胞肺癌（NSCLC）的患者的临床结局。在多种小鼠癌症模型中，发现甲羟戊酸和胆固醇抑制剂的从头合成与抗 PD-1 抗体治疗具有协同作用。在本研究中，我们研究了他汀类药物是否会影响癌细胞中程序性死亡配体 1（PD-L1）的表达。四种他汀类药物，即辛伐他汀、阿托伐他汀、洛伐他汀和氟伐他汀，可降低黑色素瘤和肺癌细胞中的 PD-L1 表达。此外，我们发现他汀类药物通过 AKT 和 β-连环蛋白信号通路抑制 PD-L1。我们的细胞和分子研究为扩展他汀类药物的临床评估以与免疫检查点抑制剂为基础的癌症治疗联合使用提供了令人鼓舞的证据。