Statins Decrease Programmed Death-Ligand 1 (PD-L1) by Inhibiting AKT and β-Catenin Signaling.
Woo-Jin LimMingyu LeeYerin OhXue-Quan FangSujin LeeChang-Hoon LimJooho ParkJi-Hong LimPublished in: Cells (2021)
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.
Keyphrases
- cardiovascular disease
- advanced non small cell lung cancer
- cancer therapy
- signaling pathway
- cell proliferation
- small cell lung cancer
- newly diagnosed
- epidermal growth factor receptor
- ejection fraction
- drug delivery
- stem cells
- type diabetes
- prognostic factors
- squamous cell carcinoma
- cross sectional
- mass spectrometry
- patient reported outcomes
- mesenchymal stem cells
- squamous cell
- amino acid
- lymph node metastasis
- low density lipoprotein