Tumour associated lymphocytes in the pleural effusions of patients with mesothelioma express high levels of inhibitory receptors

Our plain-English summary of Tumour associated lymphocytes in the pleural effusions of patients with mesothelioma express high levels of inhibitory receptors, by J. Chee, M.W. Watson, A. Chopra, et al (BMC Research Notes, 2018).

The study

• Authors: J. Chee, M.W. Watson, A. Chopra, B. Nguyen, A.M. Cook, J. Creaney, W.J. Lesterhuis, B.W. Robinson, Y.C.G. Lee, A.K. Nowak, R.A. Lake, A.M. McDonnell
• Journal: BMC Research Notes
• Published: 2018;11(1):864
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objective: Pleural effusion (PE) is a common feature of malignant pleural mesothelioma. These effusions typically contain lymphocytes and malignant cells. We postulated that the PE would be a source of lymphocytes for analysis of tumor immune milieu. The aim of this study was to compare the phenotype and T cell receptor usage of pleural effusion T cells with paired concurrently drawn peripheral blood lymphocytes. We used multi-parameter flow cytometry and high-throughput T cell receptor sequencing to analyse peripheral blood and pleural effusion mononuclear cells.

Results: Both CD8+ and CD4+ T cells from effusion showed increased expression of T cell inhibitory receptors PD-1, LAG-3 and Tim-3 compared to blood. Comprehensive T cell receptor sequencing on one of the patients showed a discordant distribution of clonotypes in the antigen-experienced (PD-1+) compartment between effusion and blood, suggesting an enrichment of antigen specific clonotypes in the effusion, with potential as an immunological response biomarker.

In plain English

This short research note from Western Australia compared T cells, a type of immune cell, in the chest fluid (pleural effusion) and blood of 9 men with malignant pleural mesothelioma, sampled at the same time. The study did not look at asbestos exposure. In the effusion, a significantly larger share of CD4+ T cells carried the inhibitory receptors PD-1, Tim-3 and LAG-3 than in blood (p = 0.004 for each). A significantly larger share of effusion CD8+ T cells carried PD-1 and LAG-3. PD-1 was the most overexpressed: the share of CD4+ and CD8+ T cells carrying it was five-fold higher in effusion than blood. In one patient, the authors sequenced T cell receptors. One dominant CD8+ clone made up 27.6% of CD8+ T cells in blood but only 1.4% in the effusion. CD4+ cells carrying PD-1 showed more clones differing between fluid and blood than CD4+ cells overall. The authors concluded their data suggest that effusion T cells, like T cells in tumours, show an exhausted pattern of raised inhibitory receptors. They noted the small numbers, the single sequenced patient, and the lack of tumour biopsies.

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: Small laboratory comparison (research note) of paired, simultaneously collected pleural effusion and blood samples, with T cell receptor sequencing in one patient
• Who was studied: 9 male patients with malignant pleural mesothelioma, studied under approval from the Sir Charles Gairdner Hospital ethics committee, Western Australia. Effusions from patients with prior talc pleurodesis or pleural infection were excluded. Study dates are not given.
• Exposure: No asbestos exposure was studied or reported for these patients. The comparison was between T cells in pleural effusion and T cells in blood.
• Main results:
  • The proportions of CD4+ and CD8+ T cells were similar in blood and effusion. For CD4+ cells: 71.9% plus or minus 10.1% in blood vs. 70.3% plus or minus 12.5% in effusion.
  • Among CD4+ T cells, a significantly larger proportion in the effusion than in blood expressed PD-1 (p = 0.004), Tim-3 (p = 0.004) and LAG-3 (p = 0.004).
  • Among CD8+ T cells, the proportion expressing PD-1 (p = 0.004) and LAG-3 (p = 0.01) was significantly higher in the effusion than in blood.
  • The proportion of CD4+ and CD8+ T cells expressing PD-1 was five-fold higher in effusion than in blood. PD-1 was the inhibitory receptor most overexpressed in effusion T cells, compared with Tim-3 and LAG-3.
  • In the single patient sequenced (patient 9), one dominant clone made up 27.6% of total CD8+ T cells in blood but only 1.4% of effusion CD8+ T cells.
  • In the same patient, the whole CD4+ population had 10 clones at higher frequency in blood and 3 higher in the effusion.
  • In the same patient, CD4+PD-1+ cells had 19 clones at higher frequency in blood and 27 higher in the effusion.
• The authors' conclusion: The authors concluded that their data suggest pleural effusion T cells, like tumour-infiltrating lymphocytes, show an exhausted phenotype, marked by more inhibitory markers than blood T cells.
• Limitations the authors state:
  • Small patient numbers, with only one patient for the T cell receptor analysis.
  • No tumour biopsies were available to compare with the effusion and blood.
  • It is not yet known what the effusion T cells target, or whether they recognize tumour antigens.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma, Pleural plaques and thickening.

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

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