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Updated: Nov 28, 2025
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
Prognostic Role of Programmed Cell Death 1 Ligand 1 in Resectable Pleural Mesothelioma
Hyun-Sung Lee1, Masatsugu Hamaji2, Nihanth Palivela1
1Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas.
Background:
The prognostic role of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM) is incompletely understood. Our objectives were to evaluate the evidence for tumor PD-L1 as a prognostic biomarker in MPM through meta-analysis and to determine whether tumor PD-L1 expression is associated with survival in MPM patients undergoing macroscopic complete resection.
Methods:
Meta-analysis was performed to determine the association of PD-L1 with overall survival in MPM (n = 1655) from 14 studies containing overall survival and tumor PD-L1 expression. Univariable and multivariable analyses tested the relationship of tumor PD-L1 with overall survival and recurrence-free survival in an institutional cohort of MPM patients treated by macroscopic complete resection (n = 75). To validate the association of PD-L1 with overall survival, we utilized two independent MPM cohorts (n = 284).
Results:
Meta-analysis demonstrated that high tumor PD-L1 expression was associated with poor overall survival. Among 75 patients undergoing macroscopic complete resection, 49 tumors (65%) expressed PD-L1 (1% or more), and high PD-L1 (50% or greater) was more commonly expressed on nonepithelial (29%) compared with epithelial tumors (14%). High tumor PD-L1 expression was independently associated with poor overall survival (P < .001, hazard ratio 5.67) and recurrence-free survival (P = .003, hazard ratio 3.28). The association of PD-L1 overexpression with unfavorable survival was more significant in epithelial MPMs than nonepithelial MPMs. These findings were validated in RNA sequencing analyses in two independent cohorts. Exploratory transcriptome analysis revealed that MPM tumors with PD-L1 overexpression displayed coexpression of other immune regulatory molecules, programmed cell death 1 ligand 2 and T-cell immunoglobulin mucin receptor 3.
Conclusions:
Tumor PD-L1 expression is a prognostic biomarker in patients undergoing surgical resection for MPM and may be useful in perioperative decision making.
Insights
High tumor programmed cell death 1 ligand 1 (PD-L1) expression indicates poor survival in malignant pleural mesothelioma (MPM) patients. This finding, confirmed by meta-analysis and patient cohorts, suggests PD-L1 is a key prognostic biomarker for MPM.
Area of Science:
- Oncology
- Immunology
- Biomarker Research
Background:
- The prognostic significance of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM) remains unclear.
- Understanding PD-L1's role is crucial for improving patient outcomes and treatment strategies.
Purpose of the Study:
- To evaluate tumor PD-L1 as a prognostic biomarker in MPM via meta-analysis.
- To determine the association between tumor PD-L1 expression and survival in MPM patients after complete surgical resection.
Main Methods:
- A meta-analysis of 14 studies (1655 patients) assessed PD-L1's association with overall survival in MPM.
- Univariable and multivariable analyses were performed on an institutional cohort (75 patients) and two independent cohorts (284 patients) for validation.
Main Results:
- Meta-analysis revealed high tumor PD-L1 expression correlates with poor overall survival.
- In resected MPM patients, high PD-L1 independently predicted poor overall survival (HR 5.67) and recurrence-free survival (HR 3.28).
- PD-L1 overexpression was linked to coexpression of PD-L2 and TIGIT, and its prognostic impact was more pronounced in epithelial MPM.
Conclusions:
- Tumor PD-L1 expression serves as a significant prognostic biomarker in MPM patients undergoing surgical resection.
- PD-L1 evaluation may aid in perioperative decision-making for MPM management.
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