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

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

Cells (2021-09-29)
Woo-Jin Lim, Mingyu Lee, Yerin Oh, Xue-Quan Fang, Sujin Lee, Chang-Hoon Lim, Jooho Park, Ji-Hong Lim
초록

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.

MATERIALS
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Sigma-Aldrich
Lonafarnib, ≥98% (HPLC)
Sigma-Aldrich
Lovastatin, Lovastatin, CAS 75330-75-5, is an anti-hypercholesterolemic agent that inhibits the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase.
Sigma-Aldrich
GGTI-2133, ≥98% (HPLC), solid
Sigma-Aldrich
Simvastatin, ≥97% (HPLC), solid