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ESMO 2014: PD-L1 protein a possible immunotherapy target in mesothelioma

In a study presented at the ESMO 2014 Congress, researchers report that about 20% of patients with malignant pleural mesothelioma have cancer cells that express a protein called programmed cell-death ligand 1 (PD-L1) that is associated with poorer outcomes.

The results suggest this population of patients could be treated with targeted therapies to PD-L1, researchers say.

The PD-L1 protein—which is part of the PD-1/PD-L1 immune pathway—is active in many different human cancers, where it is involved in suppressing the anti-tumour immune response and therefore hampering the immune system’s ability to attack the cancer.

Treatments that block this pathway are already showing considerable promise in other malignancies, such as melanoma and lung cancer, leading researchers to question whether this same pathway could be active in malignant pleural mesothelioma.

“We report that PD-L1 is expressed in 20% of malignant pleural mesothelioma patients and is associated with poor outcome, which suggests that this pathway could be targeted with PD-1/PD-L1 inhibitors,” says study author Dr Susana Cedres, from the Institut Oncològic del Vallés Consorci Hospitalari Parc Tauli, Barcelona, Spain.

Researchers analysed tissue samples from 119 patients with malignant pleural mesothelioma using an anti-PD-L1 stain. PD-L1 expression intensity was scored on a scale of 0 to 3—with ‘0’ signifying no expression, ‘1’ signifying weak expression, ‘2’ moderate, and ‘3’ strong—and then compared the score with survival data and outcomes from those patients.

They found that overall, 20.7% of patients were positive for PD-L1 expression: 18.7% of these showed strong expression of PD-L1, 25% showed moderate expression, while 56.2% showed only weak expression of PD-L1.

Most importantly, patients who were negative for PD-L1 expression survived around 11 months longer than patients who were positive for PD-L1 expression (median survival 4.79 vs 16.3 months).

Factors such as gender, smoking, asbestos exposure and disease stage did not have an effect on whether patient’s disease was positive for PD-L1 expression, but researchers did find that expression of the protein was more common in non-epithelial tumours compared to epithelial tumours.

“The results of our study could offer new treatment to this population of patients, identifying a subset of malignant pleural mesothelioma who expressed PD-L1 and could be treated with targeted therapies to PD-L1,” Cedres says.

Commenting on the two studies, Baas says that finding a good treatment for mesothelioma has been a challenge for many years and has so far led to many disappointments, so there is a need for investigation into new pathways such as the use of immune checkpoint inhibitors that target the PD-1/PD-L1 pathway.

“Cedres and colleagues’ data are important because they might help in selecting the best patients for these kinds of (expensive) therapies,” Baas says.

Some key issues need to be addressed, such as identifying the best antibody and platform to find tumours with increased expression of PD-L1, and deciding which treatment approach to take.

“It is clear from these two studies that we still have a long way to go, but proper selection of patients, improved techniques in radiotherapy and new immunotherapy treatments will help us to fight this terrible disease.”

Source: ESMO



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