Programmed cell death 1 ligand 1 expression and association with survival in mesothelioma
|Date||27 March 2014|
|Session||Proffered Papers 2 - Tumour biology and translational research|
|Citation||Journal of Thoracic Oncology (2014) 9 (Supplement 9): S7-S52. 10.1097/JTO.0000000000000131|
A.S. Mansfield1, T. Peikert2, A. Roden3, C. Krco4, S. Harrington5, H. Dong5, E. Kwon5
Due to the role Programmed Cell Death 1 Ligand 1 (PD-L1, aka B7-H1) has in establishing immune tolerance, its associations with worse survival in patients with many human malignancies, and the availability of agents to target PD-1:PD-L1 interactions, we decided to investigate the expression of PD-L1 in mesothelioma with the goal of exploring whether it might serve as a therapeutic target.
We evaluated 224 cases of malignant pleural mesothelioma (MPM) diagnosed between the years of 1986 and 2003 for the expression of PD-L1 using immunohistochemistry. These tissue samples were obtained during diagnostic surgical pleural biopsies or therapeutic resections from patients with clinically diagnosed MPM. All cases were diagnosed as MPM by a pathologist. The mouse monoclonal anti-human B7-H1 (clone 5H1-A3) antibody was used at a dilution of 1:300. The location and percent of PD-L1 expression was scored for each sample by a pathologist. Cases with less than 5% expression were considered negative. Survival between groups was compared with Kaplan-Meier curves and the log-rank test. The associations of PD-L1 expression with outcome were assessed with Cox proportional hazards regression models.
Eighty-nine of 224 samples (40%) expressed PD-L1. The median percent expression was 40% (10-70% interquartile range [IQR]). 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 tumors were less likely to be offered a therapeutic surgery due to greater extent of disease at presentation (p=0.001). Survival was significantly worse for patients with PD-L1 expression (6 months median, 4-9 mo. IQR) compared to those without PD-L1 expression (14 mo. median, 11-16 mo. IQR; p<0.0001). PD-L1 expression remained significantly associated with worse survival after adjusting for age, gender, lymphocytic infiltration, and therapeutic surgical intervention (risk ratio 1.73, 95% confidence interval 1.3-2.3; p=0.0002).
PD-L1 is expressed in a substantial proportion of MPMs and is associated with poor survival. PD-L1 expression may have important implications for the management of patients with MPM.
C. Krco: CK has patents pending in regard to B7-H1 as a prognostic marker. S. Harrington: SH has patents pending in regard to B7-H1 as a prognostic marker. H. Dong: HD has patents pending in regard to B7-H1 as a prognostic marker. E. Kwon: Both E. Kwon and the Mayo Clinic have received royalties greater from the licensing related to B7-H1. EK has patents pending in regard to B7-H1 as a prognostic marker. All other authors have declared no conflicts of interest.