Analysis of Expression of Programmed Cell Death 1 Ligand 1 (PD-L1) in Malignant Pleural Mesothelioma (MPM)

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.

Inhibition of yes‐associated protein down‐regulates PD‐L1 (CD274) expression in human malignant pleural mesothelioma

“…PD‐L1 appears to be expressed in a substantial proportion of human MPM 12, 24. Our IHC staining results also showed that 22.9% of human MPM had strong expression of PD‐L1, which indicate that some patients with MPM might benefit from anti‐PD‐1/PD‐L1 immunotherapy.…”

“…Immunotherapy targeting the immune checkpoint programmed death‐1 (PD‐1)/PD‐ligand (L) 1 axis has been used to treat various cancers including non‐small‐cell lung cancer, melanoma, renal cell carcinoma and Hodgkin lymphoma 6, 7, 8, 9, 10. Recently, PD‐1/PD‐L1 inhibitors were also used to treat patients with advanced MPM, and several clinical trials are ongoing 11, 12. Tumour PD‐L1 expression has been used as a predictive biomarker for PD‐1/PD‐L1 inhibitors 6, 12, 13.…”

“…Recently, PD‐1/PD‐L1 inhibitors were also used to treat patients with advanced MPM, and several clinical trials are ongoing 11, 12. Tumour PD‐L1 expression has been used as a predictive biomarker for PD‐1/PD‐L1 inhibitors 6, 12, 13. However, how the tumour PD‐L1 expression is regulated in cancer cells is not obvious.…”

Novel systemic therapy against malignant pleural mesothelioma

“…MPM has a high variability of lymphocytic infiltration, but prolonged survival is associated with a higher presence of lymphoid cells (170). Additionally, PD-L1 expression is variable, is associated with populations of infiltrating T cells, and may be more associated with sarcomatoid histology and a worse prognosis (171)(172)(173)(174). Multiple clinical trials have sought to determine or are currently determining if MPM responds to immune mediated therapies ( Table 2).…”

Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma

“…Expression of programmed death-ligand 1 (PD-L1) on tumor cells and TILs has been described in literature. [6][7][8][9][10][11] However, only one series described PD-1 expression on tumor-infiltrating lymphocytes (TILs) 8 and nothing has been reported yet on TIM-3 and LAG-3 in human MPM tissue.…”