Journal
CELLS
Volume 10, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/cells10092488
Keywords
statins; PD-L1; immune checkpoint inhibitor; AKT; beta-catenin
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Funding
- Konkuk University
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Studies have shown that statins can reduce PD-L1 expression in cancer cells by inhibiting the AKT and beta-catenin signaling pathways, providing compelling evidence for the clinical evaluation of combining statins with immune checkpoint inhibitors for cancer therapy.
Retrospective observational studies have reported that statins improve clinical outcomes in patients previously treated with programmed cell death protein 1 (PD-1)-targeting monoclonal anti-bodies 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 beta-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.
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