Data from the Mayo Clinic, Rochester, USA, shows that a programmed cell death 1 ligand 1 (PD-L1) is expressed in a substantial number of cases with malignant pleural mesothelioma. In addition, it is associated with poor survival. The researchers led by Dr Aaron Mansfield consider that their findings may have important implications for the management of these patients due to availability of agents that target PD-1:PD-L1 interactions. The results were presented in a proffered papers session at 4th European Lung Cancer Conference (26-29 March 2014, Geneva, Switzerland).
PD-L1 has a role in establishing immune tolerance. Its association with worse survival has been demonstrated in patients with many human malignancies. It led researchers from the Mayo Clinic to explore the expression of PD-L1 in mesothelioma. They also investigated medical records to observe whether it might serve as a therapeutic target.
A Role of PD-L1 in Malignant Pleural Mesothelioma
PD-L1 immunohistochemistry staining.
© Aaron Mansfield
By immunohistochemistry the researchers evaluated 224 cases of malignant pleural mesothelioma diagnosed in their clinic between 1986 and 2003 for the expression of PD-L1. The tissue samples were obtained during diagnostic surgical pleural biopsies or therapeutic resections from patients with clinically diagnosed malignant pleural mesothelioma. All diagnoses were confirmed by a pathologist.
They used mouse monoclonal anti-human B7-H1 (clone 5H1-A3) antibody. The location and PD-L1 expression was scored for each sample by a pathologist. Cases with less than 5% expression PD-L1 were considered negative. From 224 sample, 89 (40%) expressed PD-L1. The median expression was 40% (10-70% interquartile range).
When compared with other parameters, there were no significant differences in gender, age, decade of diagnosis, or lymphocytic infiltration between PD-L1 positive and negative patients. However, patients with PD-L1 positive tumours were less likely to be offered a therapeutic surgery due to greater extent of disease at presentation (p = 0.001).
Overall survival curve shows 14.5 months in PD-L1 negative and 5 months in PD-L1 positive patients.
© Aaron Mansfield
Survival was significantly worse for patients with PD-L1 expression (six months median, ranging from four to nine months) comparing to those without PD-L1 expression (14 months median, range 11-16 months; p < 0.0001. PD-L1 expression remained significantly associated with worse survival after adjusting for age, gender, lymphocytic infiltration, and therapeutic surgical intervention (p = 0.0002).
The authors consider that PD-L1 is expressed in a substantial number of malignant pleural mesothelioma cases in their clinic. In their dataset, it has shown to be associated with poor survival. Due to the availability of drugs targeting PD-L1, it may be considered important in future management opportunities in these patients.
Reference
Abstract 127O: Programmed cell death 1 ligand 1 expression and association with survival in mesothelioma.
The study co-authors Krco, Harrington, Dong, and Kwon have patents pending in regard to B7-H1 as a prognostic marker. Dr Kwon and the Mayo Clinic have received royalties from the licensing related to B7-H1. All other authors have declared no conflicts of interest.
The European Lung Cancer Conference (ELCC) is organised by the European Society for Medical Oncology (ESMO) and the International Association for the Study of Lung Cancer (IASLC). During the four-day programme, attendees benefit from educational and scientific updates provided by thoracic oncology specialists on different multidisciplinary topics important for research and clinical practice in the field of lung cancer.