Comparative analysis of malignant pleural effusion and peripheral blood reveals unique T cell signatures associated with survival in mesothelioma patients

Our plain-English summary of Comparative analysis of malignant pleural effusion and peripheral blood reveals unique T cell signatures associated with survival in mesothelioma patients, by N. Principe, K.L.P. Stevens, A.L. Phung, et al (Oxford Open Immunology, 2026).

The study

• Authors: N. Principe, K.L.P. Stevens, A.L. Phung, M. McCoy, J. Kidman, A. Ismail, A.M. Cook, A. Chopra, M. Watson, B.W. Robinson, J. Creaney, Y.C.G. Lee, J. Waithman, W.J. Lesterhuis, R.A. Lake, A.K. Nowak, J. Chee, A.M. McDonnell
• Journal: Oxford Open Immunology
• Published: 2026;7(1):iqaf008
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The success of cancer immunotherapies has highlighted the importance of monitoring the anti-tumour T cell response. Patients with mesothelioma frequently present with a malignant pleural effusion (MPE) that is commonly drained regularly to alleviate symptoms. As MPE contains tumour cells, T cells and cytokines, it provides a unique opportunity to sample immune events at the tumour site. However, there is minimal information on how MPE T cells are distinct from those in the blood, and whether T cell phenotypes unique to each compartment correlate with survival. We characterised T cell populations of matched MPE and blood from 31 mesothelioma patients using flow cytometry and bulk T cell receptor beta (TCRβ) sequencing. MPE CD8+ and CD4+ T cells displayed increased expression of PD-1, TIGIT, LAG-3 and TIM-3 compared to blood, with co-expression of inhibitory receptors greatest on MPE CD8+ T cells with a tissue resident memory T cell phenotype (CD69+CD103+). CD8+ TCRβ repertoires displayed clonal overlap between MPE and blood, suggesting that a majority of T cells traffic between these compartments. Finally, we show that high expression of PD-1 on circulating CD4+ T cells is an independent prognostic factor for poor survival in this patient group. This work suggests that MPE T cell phenotypes differ from those in circulation, with blood-based T cell subsets more sensitive predictors of outcome in this study.

© The Author(s) 2025. Published by Oxford University Press.

In plain English

This laboratory study compared T cells, a type of immune cell, in matched samples of blood and of fluid built up around the lungs (malignant pleural effusion). Samples came from 31 pleural mesothelioma patients enrolled from August 2014 to February 2018. With three exceptions, samples predated any treatment. The article did not examine asbestos exposure. Effusion T cells more often carried inhibitory receptors (PD-1, TIGIT, TIM-3 and LAG-3) than blood T cells, and tissue-resident memory T cells appeared only in the effusion. On average, 48.6% of CD8-positive PD-1-positive T cell clones in the effusion were also found in blood. The authors took this to suggest these cells travel between the sites. More blood than effusion T cell features were linked to survival. In one combined model, older age, higher platelet count and a higher share of blood CD4-positive T cells carrying PD-1 were independently linked to poorer survival. In a second model, the same held for age, platelet count and blood CD4-positive T cells carrying both PD-1 and TIGIT. The authors noted that samples came from one time point and said the PD-1 finding warrants validation in a larger cohort.

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: Laboratory comparison of matched blood and malignant pleural effusion samples, using flow cytometry and T cell receptor (TCR beta) sequencing, with an exploratory survival analysis
• Who was studied: 31 patients with pleural mesothelioma (28 men, 3 women; median age 68, range 30 to 89; 27 epithelioid-containing, 3 sarcomatoid, 1 unspecified subtype), enrolled August 2014 to February 2018. All but three had no treatment before sampling. TCR sequencing was done on samples from 11 of these patients.
• Exposure: No asbestos exposure was studied. The study measured T cell types and markers in the pleural effusion compared with blood.
• Main results:
  • In the effusion, PD-1 was the main inhibitory receptor on both CD8 and CD4 T cells. The share of T cells carrying PD-1, TIGIT, TIM-3 or LAG-3 was significantly greater in the effusion than in blood.
  • The effusion had significantly greater proportions of regulatory T cells and of central memory CD8 and CD4 T cells than matched blood. Terminally differentiated effector memory T cells were significantly lower in the effusion.
  • Two tissue-resident memory T cell groups were found only in the effusion, not in the blood.
  • In the 11 sequenced patients, a mean of 48.6% (SD 22.6%) of CD8 PD-1-positive T cell clones in the effusion were also present in matched blood. For CD4 PD-1-positive clones the figure was 16.6% (SD 11.1%).
  • More T cell features in blood than in effusion were associated with overall survival on single-variable analysis. Only three effusion features were significant.
  • Patients with more than 6.78% naive CD8 T cells in blood had a median survival of 19 months. Patients below that level had a median survival of 6 months.
  • On single-variable analysis, the percentage of blood CD4 T cells carrying PD-1 (measured as a continuous value) had a hazard ratio of 1.05 (95% CI 1.00 to 1.10, p = 0.041).
  • In multivariate model 1, three factors were independent prognostic factors for poor survival: age at diagnosis, platelet count, and the proportion of blood CD4 T cells carrying PD-1.
  • In multivariate model 2, three factors were independent prognostic factors for poor overall survival: age at diagnosis, platelet count, and the proportion of blood CD4 T cells carrying both PD-1 and TIGIT.
  • T cell receptor repertoire diversity (DE50) in blood or effusion showed no significant correlation with overall survival.
• The authors' conclusion: The authors concluded that effusion T cells differ from those in blood and that the effusion offers a source for tracking anti-tumour T cell responses. They found that blood-based T cell features were more sensitive predictors of outcome in this study. They said the finding that PD-1 on circulating CD4 T cells is prognostic for poor survival warrants validation in a larger cohort.
• Limitations the authors state:
  • Samples were collected at a single time point only.
  • The study did not include in-depth analyses of T cell function.
  • Other immune cells, which could influence the results, were not studied.
  • Most patients did not receive anti-PD-1 treatment, so the link between PD-1-positive T cells and response to that treatment could not be assessed.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Mesothelioma, Cytokine.

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