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Published on: August 11, 2018
Defect in recruiting effector memory CD8+ T-cells in malignant pleural effusions compared to normal pleural fluid
Arnaud Scherpereel1, Bogdan Dragos Grigoriu, Marc Noppen
1INSERM Unit 1019, CIIL, Institut Pasteur de Lille, Lille, France. arnaud.scherpereel@chru-lille.fr
Background:
Malignant pleural effusions (MPE) are a common and fatal complication in cancers including lung or breast cancers, or malignant pleural mesothelioma (MPM). MPE animal models and immunotherapy trials in MPM patients previously suggested defects of the cellular immunity in MPE. However only few observational studies of the immune response were done in MPM patients, using questionable control groups (transudate…).
Methods:
We compared T cell populations evaluated by flow cytometry from blood and pleural effusion of untreated patients with MPM (n = 58), pleural metastasis of adenocarcinoma (n = 30) or with benign pleural lesions associated with asbestos exposure (n = 23). Blood and pleural fluid were also obtained from healthy subjects, providing normal values for T cell populations.
Results:
Blood CD4+ or CD8+ T cells percentages were similar in all groups of patients or healthy subjects. Whereas pleural fluid from healthy controls contained mainly CD8+ T cells, benign or malignant pleural effusions included mainly CD4+ T cells. Effector memory T cells were the main T cell subpopulation in pleural fluid from healthy subjects. In contrast, there was a striking and selective recruitment of central memory CD4+ T cells in MPE, but not of effector cells CD8+ T cells or NK cells in the pleural fluid as one would expect in order to obtain an efficient immune response.
Conclusions:
Comparing for the first time MPE to pleural fluid from healthy subjects, we found a local defect in recruiting effector CD8+ T cells, which may be involved in the escape of tumor cells from immune response. Further studies are needed to characterize which subtypes of effector CD8+ T cells are involved, opening prospects for cell therapy in MPE and MPM.
Insights
Malignant pleural effusions show a defect in CD8+ T cell recruitment, hindering anti-tumor immunity. This finding suggests potential new cell therapies for malignant pleural mesothelioma (MPM) and other cancers.
Area of Science:
- Immunology
- Oncology
- Cellular Biology
Background:
- Malignant pleural effusions (MPE) are a fatal complication of cancers like lung cancer, breast cancer, and malignant pleural mesothelioma (MPM).
- Previous research suggested cellular immunity defects in MPE, but studies in MPM patients were limited and used inadequate control groups.
- Understanding the immune microenvironment in MPE is crucial for developing effective treatments.
Purpose of the Study:
- To investigate and compare T cell populations in the pleural fluid and blood of patients with MPE and benign pleural conditions.
- To identify specific immune cell deficits that may contribute to tumor cell survival in the pleural space.
- To establish a baseline for immune cell distribution in healthy pleural fluid for comparison.
Main Methods:
- Flow cytometry was used to analyze T cell populations in blood and pleural effusion samples.
- Patients included those with untreated MPM (n=58), pleural metastasis of adenocarcinoma (n=30), and benign pleural lesions (n=23).
- Samples from healthy subjects were used to establish normal T cell population values.
Main Results:
- While blood T cell percentages were similar across groups, pleural fluid composition differed significantly.
- Healthy pleural fluid predominantly contained CD8+ T cells, whereas MPE and benign effusions had mainly CD4+ T cells.
- MPE showed a selective recruitment of central memory CD4+ T cells, with a notable absence of effector CD8+ T cells and NK cells.
Conclusions:
- A local defect in effector CD8+ T cell recruitment was identified in MPE, potentially facilitating tumor cell immune evasion.
- This impaired immune response in the pleural space highlights a critical area for therapeutic intervention.
- Further research into specific effector CD8+ T cell subtypes could pave the way for novel cell therapies for MPE and MPM.
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