Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM).

Susana Cedrés,Jon Zugazagoitia,Alex Martinez-Marti,Pablo Martinez,Enriqueta Felip,Ana Enguita,Alejandro Navarro-Mendivil,Santiago Ponce-Aix,Irene Sansano,Nupur Gangopadhyay

doi:10.1371/journal.pone.0121071

Abstract

BackgroundThe increasing incidence and poor outcome associated with MPM requires finding effective treatment for this disease. PD1/PD-L1 pathway plays a central role in tumor immune evasion and appears to be predictive and prognostic marker. PD-L1 is expressed in many different human cancers but its role in MPM has yet to be established. The aim of this study is to evaluate the expression of PD-L1 in MPM.Methods119 MPM patients (p) from two institutions between November 2002 and February 2014 were reviewed. Formalin-fixed, paraffin-embedded tissue was stained with anti-PD-L1 (clone E1L3N). Cases showing more than 1% of tumor cells expression of PD-L1 were considered positive.ResultsPD-L1 was analyzed in 77 p with tumor tissue available and was positive in 20.7% p (14 samples in membrane, 16 in cytoplasm and 4 in immune infiltrate). PD-L1 intensity was weak in 56.2%, moderate in 25% and strong in 18.7% p. There was a significant relationship between PD-L1 expression and histology (PD-L1 expression 37.5% in no-epithelioid tumor and 13.2% in epithelioid; p=0.033). The median survival in p PD-L1 positive was 4.79 vs 16.3 months in p PD-L1 negative (p=0.012).ConclusionsWe have shown PD-L1 is expressed in 20% of patients, associated with no epithelioid histology and poor prognostic in MPM. Our results suggest PD-L1 warrants further exploration in selecting p for immunotherapy.

Highlights

Malignant pleural mesothelioma (MPM) is a locally aggressive malignancy arising from the mesothelial cells lining the pleura with a median survival time for untreated patients ranging from 4 to 12 months [1]
There was a significant relationship between Programmed Cell Death 1 Ligand 1 (PD-L1) expression and histology (PD-L1 expression 37.5% in no-epithelioid tumor and 13.2% in epithelioid; p=0.033)
We have shown PD-L1 is expressed in 20% of patients, associated with no epithelioid histology and poor prognostic in MPM

Summary

Introduction

Malignant pleural mesothelioma (MPM) is a locally aggressive malignancy arising from the mesothelial cells lining the pleura with a median survival time for untreated patients ranging from 4 to 12 months [1]. The current standard for systemic treatment of advanced MPM is the combination of chemotherapy with cisplatin and folate drugs analogs, but treatment results in an improvement in median survival of less than 3 months [2,3]. Multimodality therapy with chemotherapy, surgery and radiation therapy has been shown to potentially improve survival in a highly selected group of patients with MPM [4,5]. The increasing incidence and poor outcome associated with MPM require urgently novel therapeutic strategies to improve the prognosis. The increasing incidence and poor outcome associated with MPM requires finding effective treatment for this disease. The aim of this study is to evaluate the expression of PD-L1 in MPM

Objectives

Results

Conclusion