Mesothelioma patients with higher levels of the PD-L1 protein in their tumor cells have worse overall survival compared to those with lower levels. But that may not be true for patients who have immunotherapy.
That news comes from a new European study of more than 200 patients. PD-L1 and its partner protein PD-1 (found in immune system cells) are popular targets for new immunotherapy drugs.
But the new study aimed to find out if they impact mesothelioma survival independently of immunotherapy. The team concluded the PD-L1 protein may shorten lifespan. PD-1 does not seem to have the same effect.
Pleural Mesothelioma and the PD-L1 Protein
Pleural mesothelioma is an intractable cancer of the lung lining. It often leads to poor outcomes. Cancer researchers around the world want to know what makes mesothelioma so tough and how to get around its defenses.
PD-L1/PD-1 is one way that mesothelioma defends itself. The full name for the PD-L1 protein is programmed death ligand 1. PD-1, which most often occurs in immune system cells, stands for programmed cell death 1.
This protein is part of an immune-checkpoint blockade. In healthy people, it helps keep the immune system from attacking things it is not supposed to. But in some mesothelioma patients, this protein protects the cancer cells instead. It makes them even harder to kill.
Immune checkpoint inhibitors are drugs that undermine the protective power of the PD-1/PD-L1 protein. The drugs Keytruda and Opdivo are examples of PD-1/PD-L1 blockers. When this protein cannot do its job, mesothelioma cells are more vulnerable to attack.
Checkpoint Inhibitors and Survival
The new study involved researchers from Austria, Croatia, Slovenia, Hungary, Germany, and the Czech Republic. They examined tumor samples from 203 pleural mesothelioma patients. The samples came from five European cancer centers. The researchers used immunohistochemistry to measure the PD-1/PD-L1 protein levels in each sample.
Eighteen patients had PD-L1 levels in their tumor cells above 10 percent. About a quarter of patients had PD-1 levels in their TILS (tumor-infiltrating lymphocytes) cells over 10 percent. There was no relationship between the PD-1/PD-L1 protein expression or with mesothelioma subtype or stage.
But there was a relationship between PD-L1 expression and survival. Patients with a tumor cell (TC) PD-L1 protein level over 10 percent survived for a median of 6.3 months. For those with lower TC PD-L1 expression, median overall survival was 15.1 months.
There was no correlation between elevated PD-L1 or PD-1 in the TILS cells.
“In this multicenter cohort study, we demonstrate that high (>10%) PD-L1 expression of TCs independently predicts worse overall survival in malignant pleural mesothelioma,” writes Luka Brcic of Austria’s Medical University of Graz.
The patients in this study did not receive immunotherapy. Immunotherapy is a growing field of study for mesothelioma researchers. But not all patients respond to it. Dr. Brcic says the PD-1/PD-L1 protein could hold the key.
“Further studies are warranted to investigate the value of PD-L1/PD-1 expression as a marker for treatment response in pleural mesothelioma patients receiving immunotherapy,” he writes.
Brcic, L, et al, “Prognostic impact of PD-1 and PD-L1 expression in malignant pleural mesothelioma: an international multicenter study”, Translational Lung Cancer Research, April 2021, https://tlcr.amegroups.com/article/view/50434/html