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Updated: Feb 19, 2026
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
Molecular and Histopathological Characterization of the Tumor Immune Microenvironment in Advanced Stage of Malignant
Namrata S Patil1, Luisella Righi2, Hartmut Koeppen1
1Oncology Biomarkers Development, Genentech, Inc., South San Francisco, California.
Introduction:
Malignant pleural mesothelioma (MPM) is a rare, highly aggressive, and relatively chemoresistant and radioresistant malignancy with limited therapeutic options. Our objective was to investigate the prevalence of programmed death ligand 1 (PD-L1) and the characteristics of the immune environment in this disease.
Methods:
A total of 99 archival tumors from advanced-stage MPM were immunohistochemically tested in parallel for PD-L1 in two different laboratories, and 87 of them were profiled for immune gene expression by NanoString analysis for 800 genes. A prior study on the same samples indicated a low mutational load with a complex mutational landscape of genetic variations more frequently associated with the p53/DNA repair and phosphoinisitide-3-kinase pathways.
Results:
PD-L1 expression was found in 16% of the MPM tumor samples, either in the tumor cells or the infiltrating immune cells. Gene expression analysis suggested that MPM is an inflamed tumor type and can be classified into three different subgroups on the basis of the different expression profiles of immune-related genes, of which two groups showed varying degrees of expression of immune-related genes. Overall, these molecular findings suggest that these subgroups of MPM associated with PD-L1 positivity and expression of immune-related genes accounting for 60% of MPMs represent a candidate subtype that may respond to cancer immunotherapy.
Conclusions:
These data suggest that 60% of patients with MPM characterized by either PD-L1 expression or an inflamed status are attractive candidates for cancer immunotherapeutic options.
Insights
Programmed death ligand 1 (PD-L1) and immune gene expression were investigated in malignant pleural mesothelioma (MPM). 60% of MPM patients with PD-L1 expression or inflamed status may benefit from immunotherapy.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer with limited treatment options.
- MPM exhibits resistance to chemotherapy and radiotherapy.
- Investigating the tumor immune microenvironment is crucial for novel therapeutic strategies.
Purpose of the Study:
- To determine the prevalence of programmed death ligand 1 (PD-L1) in MPM.
- To characterize the immune environment of MPM.
- To identify potential candidates for cancer immunotherapy.
Main Methods:
- Immunohistochemistry was used to detect PD-L1 expression in 99 MPM tumor samples.
- NanoString analysis profiled immune gene expression in 87 MPM samples.
- Analysis included 800 immune-related genes.
Main Results:
- PD-L1 expression was observed in 16% of MPM tumors.
- MPM was identified as an inflamed tumor type.
- Three distinct immune gene expression subgroups were identified, with two showing significant immune-related gene expression.
Conclusions:
- 60% of MPM patients exhibit either PD-L1 expression or an inflamed tumor status.
- These patients represent a promising candidate group for cancer immunotherapy.
- Findings suggest immunotherapy as a viable option for a significant proportion of MPM patients.
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