Statin Drugs Support Immunotherapy for Mesothelioma, New Study Finds

There’s more evidence that statin drugs may improve the effectiveness of mesothelioma immunotherapy. 

The new study, led by Korean biochemists, is not the first to show that these anti-cholesterol medications may help mesothelioma patients. But this one goes a step further to explain why they help. 

Researchers focused on the impact of statin drugs on PD-1 expression. PD-1 is a protein that protects mesothelioma cells against immune system attack. 

The findings suggest that, by lowering PD-1 levels, anti-cholesterol drugs may play a greater role in the future of mesothelioma treatment. 

PD-1 and Mesothelioma Immunotherapy

PD-1 is an immune checkpoint protein that occurs on the surface of cells. Normally, it helps keep the immune system from attacking healthy tissues. But mesothelioma cells and some other types of cancer can produce extra PD-1. This allows them to “trick” the immune system into letting them grow unchecked. 

PD-1 has been a focus for cancer researchers for the past several years. Drugs like Keytruda (pembrolizumab) and Imfinzi (durvalumab) are examples of PD-1 inhibitors. 

Statin drugs are not normally cancer medications. Lipitor and Pravachol are examples of statin medications. Many people take statins to help lower their cholesterol. 

But several studies show that statins may also improve outcomes for cancer patients. This is especially true for patients on anti-PD-1 drugs. The new Korean study offers further evidence for the value of this approach. 

How Statin Drugs May Enhance Immunotherapy Treatment

Statin drugs have been the subject of several cancer studies. These medications have some pro-apoptotic properties. This means that they can trigger the dying process in certain cells. 

Unfortunately, they do not seem to be able to kill mesothelioma cells by themselves. A 2014 Australian study found that the statin drug atorvastatin had no effect on malignant mesothelioma. 

But another study that same year showed that statin drugs helped the chemotherapy drug Alimta (pemetrexed) work better. More mesothelioma cells died with the combination treatment than with Alimta alone. 

The new Korean study found a synergistic effect between statin drugs and anti-PD-1 therapy. The team tested four popular statin drugs on melanoma and lung cancer cells. They found that the drugs lowered the level of PD-1 expressed by these cells. The suppression had an impact on other signaling proteins, too. 

Lower PD-1 could make mesothelioma cells more susceptible to immune system attack. The research team calls the findings “inspiring”. 

“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,” the report concludes. 

More research is needed before doctors will know the best way to incorporate statin drugs into mesothelioma treatment. In the meantime, mesothelioma patients who are on these medications should follow their doctor’s advice regarding their use during treatment.

Source:

Lim, WJ, et al, “Statins Decrease Programmed Death-Ligand 1 (PD-L1) by Inhibiting AKT and β-Catenin Signaling”, September 20, 2021, Cells, https://www.mdpi.com/2073-4409/10/9/2488