Defect in recruiting effector memory CD8+ T-cells in malignant pleural effusions compared to normal pleural fluid

Our plain-English summary of Defect in recruiting effector memory CD8+ T-cells in malignant pleural effusions compared to normal pleural fluid, by A. Scherpereel, B.D. Grigoriu, M. Noppen, et al (BMC Cancer, 2013).

The study

• Authors: A. Scherpereel, B.D. Grigoriu, M. Noppen, T. Gey, B. Chahine, S. Baldacci, J. Trauet, M.C. Copin, J.P. Dessaint, H. Porte, M. Labalette
• Journal: BMC Cancer
• Published: 2013;13:324
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

In plain English

This French study compared immune cells in blood and in the fluid around the lungs (pleural fluid). The authors recruited 147 consecutive patients from 19 hospitals with a pleural effusion suspected to be malignant pleural mesothelioma. Biopsies showed 79 had malignant pleural mesothelioma, 38 pleural metastasis of adenocarcinoma, and 30 benign pleural lesions associated with asbestos exposure. Fifteen otherwise healthy adults having thoracoscopic treatment for severe essential hyperhidrosis (excessive sweating) provided normal pleural fluid.

In healthy pleural fluid, CD8+ T cells predominated (median CD4+/CD8+ ratio 0.59). In every patient group CD4+ T cells predominated, with median ratios of 3.8 (metastasis), 3.2 (benign asbestos-related lesions) and 2.2 (mesothelioma). Effector memory cells were a median 84.7% of CD8+ T cells in healthy fluid but 16.1% to 19.7% in patient groups. Natural killer (NK) cells made up a much smaller share of pleural lymphocytes in all patient groups than in healthy subjects.

The authors concluded that there is a local defect in recruiting effector CD8+ T cells, which may help tumor cells escape the immune response. The abstract gives different group sizes from the methods.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Prospective multicenter study comparing immune cell populations, measured by flow cytometry, in paired blood and pleural fluid samples
• Who was studied: 147 consecutive untreated patients from 19 hospitals in the North of France with a pleural effusion suspected of malignant pleural mesothelioma. Final diagnoses were 79 malignant pleural mesothelioma, 38 pleural metastasis of adenocarcinoma, and 30 benign pleural lesions associated with asbestos exposure. Controls were 15 otherwise healthy adults with severe essential hyperhidrosis whose pleural fluid was obtained by pleural lavage.
• Exposure: The study did not measure fiber type or dose. Asbestos exposure was recorded as yes in 11 (29%) of the metastasis group, 24 (80%) of the benign asbestos-related lesion group and 61 (77.2%) of the mesothelioma group.
• Main results:
  • Median pleural fluid CD4+/CD8+ ratios were as follows. Metastasis group: 3.8 (IQR 2.6 to 4.8). Benign asbestos-related lesion group: 3.2 (2.2 to 4.5). Mesothelioma group: 2.2 (1.5 to 2.9). Healthy subjects: 0.59 (0.48 to 0.67).
  • Proportions of CD4+ and CD8+ T cells in blood were very similar in healthy subjects and in all patient groups (data not shown).
  • Effector memory cells as a median percentage of pleural CD8+ T cells were as follows. Metastasis group: 19.7 (IQR 4.3 to 45.3). Benign asbestos-related lesion group: 16.1 (10.7 to 36). Mesothelioma group: 18.6 (5.6 to 49.2). Healthy subjects: 84.7 (83.1 to 87). The authors reported this difference from normal fluid as significant.
  • In all patient groups, naive and central memory cells were the main subsets among pleural CD4+ T cells. Median central memory CD4+ percentages were 47.4 (metastasis), 53.5 (benign asbestos-related lesions) and 40.5 (mesothelioma), versus 13.1 in healthy subjects.
  • The relative proportion of NK cells in pleural fluid was much lower in all patient groups than in healthy controls (p less than 0.001). Median percentages of total lymphocytes were 3.5 (metastasis), 2.8 (benign asbestos-related lesions), 10 (mesothelioma) and 16.0 (healthy). Mesothelioma patients kept relatively more pleural NK cells than the other two patient groups.
  • Pleural fluid from mesothelioma patients contained fewer naive and central memory CD8+ T cells than pleural fluid from asbestos-exposed patients without mesothelioma (p less than 0.05 or less).
  • Regulatory T-cell data were available for only 23 paired specimens. These cells showed no significant difference among the 4 groups (p = 0.17).
  • Percentages of total CD8+ T cells or CD8+ subsets measured before treatment were not associated with survival in a Cox proportional hazards model (data not shown).
• The authors' conclusion: The authors concluded that, compared with normal pleural fluid, malignant pleural effusions show a local defect in recruiting effector CD8+ T cells, which may be involved in tumor cells escaping the immune response.
• Limitations the authors state:
  • The authors stated that firm conclusions about regulatory T cells are difficult because of the very limited number of patients in each subgroup.
  • The interquartile range for regulatory T cells in the mesothelioma group could not be calculated because of the low number of cases.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Pleural Mesothelioma, Immunotherapy, Metastasis, Adenocarcinoma, Asbestos Exposure.

Related studies

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• Efficacy of nivolumab and ipilimumab in patients with malignant pleural mesothelioma is related to a subtype of effector memory cytotoxic T cells: Translational evidence from two clinical trials — J.M. Mankor, M.J. Disselhorst, et al. (2020)
• Longitudinal Measurement of Pleural Fluid Biochemistry and Cytokines in Malignant Pleural Effusions — R. Thomas, H.M. Cheah, et al. (2016)
• Calretinin. A selective marker of normal and neoplastic mesothelial cells in serous effusions — M.C. Barberis, M. Faleri, et al. (1997)
• Malignant pleural fluid from mesothelioma has potent biological activities — H.M. Cheah, S.M. Lansley, et al. (2017)
• Expression Profiles of Cytokine mRNAs in the Pleural Fluid Reveal Differences Among Tuberculosis, Malignancies, and Pneumonia-Exudative Pleural Effusions — D.L. Espósito, V.R. Bollela, et al. (2015)

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