PD-L1 is an acronym for “programmed death-ligand 1.” The grim name is fitting, as this cancerous protein is linked to mesothelioma.

It’s also connected to poor prognosis, with a higher PD-L1 volume often leading to worse survival.

So it’s the task of doctors and researchers to confront this protein, which has led to the rise of immunotherapy for mesothelioma.

A new report published in the Annals of Thoracic Surgery highlighted the association between PD-L1 and low survival rates, even for patients undergoing surgery. The authors, which included Baylor St. Luke’s Medical Center thoracic surgeon Dr. Taylor Ripley, analyzed 75 complete macroscopic resection cases.

PD-L1 subdues the body’s immune system. More specifically, the protein connects with a protein receptor on T-cells called PD-1. This bond makes the T-cells, the immune system’s guards against viruses and diseases, ineffective against mesothelioma.

A weakened immune system allows mesothelioma cells to replicate and spread freely in the body. This unrestrained growth will overwhelm the body quickly, resulting in poor survival.

 

How Much Does PD-L1 Impact Mesothelioma Survival?

In the study mentioned above, the 75 surgery cases included some level of PD-L1 expression. Fewer than half had what is considered “high PD-L1 expression,” but those cases resulted in significantly worse survival.

In fact, more than 80% of the patients with a high PD-L1 expression had a worse survival than those not meeting this criteria. Around 70% of high PD-L1 patients had worse recurrence-free survival.

“These findings were validated in RNA sequencing analyses in two independent cohorts,” the authors wrote. They added that high PD-L1 usually results in high levels of other cancerous proteins that block the immune system.

This study analyzed patients who had surgery. The impact of PD-L1 is often the same for unresectable cases: worse survival due to an inactive immune system.

Fortunately, one therapeutic option explicitly targets this protein.

 

How to Stop PD-L1 in Mesothelioma

Immunotherapy is slowly becoming at least on par with chemotherapy as a cancer treatment. The most popular type of immunotherapy, checkpoint inhibitor drugs, explicitly target PD-L1.

The U.S. Food and Drug Administration approved Opdivo and Yervoy, two checkpoint inhibitors, for mesothelioma earlier in 2020. Opdivo, the brand name for nivolumab, is an anti-PD-L1 drug.

The FDA also approved Keytruda in mesothelioma cases involving high levels of PD-L1. Keytruda, the brand name for pembrolizumab, is another anti-PD-L1 immunotherapy option.

These drugs often outperform chemotherapy for mesothelioma. Opdivo with Yervoy has a median survival of 18 months, which is four months better than chemotherapy. Keytruda has similar improvement for PD-L1 cases.

 

Will Immunotherapy Work Before or After Surgery for Mesothelioma?

Immunotherapy is currently only approved for mesothelioma when surgery is off the table. The approval could expand, though.

Since the survival rates are low when PD-L1 expression is high, especially for surgery cases, immunotherapy drugs like Opdivo and Keytruda can be utilized before or after an operation.

One clinical trial is actually testing both. Dr. Patrick Forde and his team at Johns Hopkins in Baltimore, Maryland, are using Opdivo and Yervoy starting six weeks before surgery. Patients have the option of resuming the therapy after their operation. Another trial is using Opdivo plus chemotherapy before surgery.

This method enhances the immune system in the cancer’s earliest stages. Doctors hope the T-cells slow the disease growth, allowing a larger percentage to be removed during surgery. The enhanced immune system again benefits if the anti-PL-L1 therapy continues after surgery.

Both clinical trials are accepting new patients. Please reach out to our medical team if you want to learn more about how immunotherapy can improve survival. We can also get you a second opinion for your diagnosis, which may reveal whether you have a high PD-L1 expression. Email our lead patient advocate and registered nurse, Jenna Campagna, at jenna@mesotheliomaguide.com.

    Sources & Author

Devin Goldan image

About the Writer, Devin Golden

Devin Golden is the content writer for Mesothelioma Guide. He produces mesothelioma-related content on various mediums, including the Mesothelioma Guide website and social media channels. Devin's objective is to translate complex information regarding mesothelioma into informative, easily absorbable content to help patients and their loved ones.

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    Sources & Author

Picture of Devin Golden

About the Writer, Devin Golden

Devin Golden is the content writer for Mesothelioma Guide. He produces mesothelioma-related content on various mediums, including the Mesothelioma Guide website and social media channels. Devin's objective is to translate complex information regarding mesothelioma into informative, easily absorbable content to help patients and their loved ones.