Abstract

BackgroundMalignant 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…).MethodsWe 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.ResultsBlood 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.ConclusionsComparing 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.

Highlights

  • Malignant pleural effusions (MPE) are a common and fatal complication in cancers including lung or breast cancers, or malignant pleural mesothelioma (MPM)

  • The final pathological diagnosis split the patients into three groups: 38 patients with pleural metastasis of adenocarcinoma (METS group), 30 patients with benign pleural lesions associated with asbestos exposure (BPLAE group), and 79 patients with malignant pleural mesothelioma (MPM group) (Table 1)

  • CD4+ T cells represented the major T-cell population in peripheral blood, while CD8+ T cells constituted the major population in normal pleural fluid (Figure 1A and F), resulting in a CD4/CD8 ratio in pleural fluid

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Summary

Introduction

Malignant pleural effusions (MPE) are a common and fatal complication in cancers including lung or breast cancers, or malignant pleural mesothelioma (MPM). Pleural metastases and/or MPE are mostly of lung cancer (15-30%), breast cancer (10-15%) or lymphomas origin. These patients ongoing clinical trials [4,5,6,7,8,9,10]. Previous studies never compared pleural cell populations from MPM patients with those of healthy subjects, but instead used various control groups such as pleural transudates, tuberculous effusions or ascites, none of which could provide accurate baseline values [18,19,20]

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