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

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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.

Original languageEnglish
Article number864
Number of pages6
JournalBMC Research Notes
Volume11
Issue number1
DOIs
Publication statusPublished - 5 Dec 2018

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Lymphocytes
Mesothelioma
Pleural Effusion
Tumors
Blood
T-Cell Antigen Receptor
T-cells
Neoplasms
Costimulatory and Inhibitory T-Cell Receptors
T-Lymphocytes
Antigens
Flow cytometry
Biomarkers
Flow Cytometry
Throughput
Phenotype

Cite this

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title = "Tumour associated lymphocytes in the pleural effusions of patients with mesothelioma express high levels of inhibitory receptors",
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.",
keywords = "Mesothelioma, Pleural effusion, T cell receptor",
author = "Jonathan Chee and Watson, {Mark W.} and Abha Chopra and Bella Nguyen and Cook, {Alistair M.} and Jenette Creaney and Lesterhuis, {Willem J.} and Robinson, {Bruce W.} and {Gary Lee}, {Y. C.} and Nowak, {Anna K.} and Lake, {Richard A.} and McDonnell, {Alison M.}",
year = "2018",
month = "12",
day = "5",
doi = "10.1186/s13104-018-3953-x",
language = "English",
volume = "11",
journal = "BMC Research Notes",
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TY - JOUR

T1 - Tumour associated lymphocytes in the pleural effusions of patients with mesothelioma express high levels of inhibitory receptors

AU - Chee, Jonathan

AU - Watson, Mark W.

AU - Chopra, Abha

AU - Nguyen, Bella

AU - Cook, Alistair M.

AU - Creaney, Jenette

AU - Lesterhuis, Willem J.

AU - Robinson, Bruce W.

AU - Gary Lee, Y. C.

AU - Nowak, Anna K.

AU - Lake, Richard A.

AU - McDonnell, Alison M.

PY - 2018/12/5

Y1 - 2018/12/5

N2 - 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.

AB - 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.

KW - Mesothelioma

KW - Pleural effusion

KW - T cell receptor

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U2 - 10.1186/s13104-018-3953-x

DO - 10.1186/s13104-018-3953-x

M3 - Article

VL - 11

JO - BMC Research Notes

JF - BMC Research Notes

SN - 1756-0500

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