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

Abstract

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.

• Authors: Woo-Jin Lim, Mingyu Lee, Yerin Oh, Xue-Quan Fang, Sujin Lee, Chang-Hoon Lim, Jooho Park, Ji-Hong Lim
• Journal: Cells (Cells) Vol. 10 Issue 9 (09 20 2021) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 34572136 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• B7-H1 Antigen
• CD274 protein, human
• CTNNB1 protein, human
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• beta Catenin
• Proto-Oncogene Proteins c-akt

Topics

• Apoptosis
• B7-H1 Antigen (antagonists & inhibitors)
• Cell Proliferation
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Neoplasms (drug therapy, genetics, metabolism, pathology)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors)
• Tumor Cells, Cultured
• beta Catenin (antagonists & inhibitors)