Functional properties of CD8(+) lymphocytes in patients with pleural plaque and malignant mesothelioma

Our plain-English summary of Functional properties of CD8(+) lymphocytes in patients with pleural plaque and malignant mesothelioma, by N. Kumagai-Takei, Y. Nishimura, M. Maeda, et al (Journal of Immunology Research, 2014).

The study

• Authors: N. Kumagai-Takei, Y. Nishimura, M. Maeda, H. Hayashi, H. Matsuzaki, S. Lee, T. Kishimoto, K. Fukuoka, T. Nakano, T. Otsuki
• Journal: Journal of Immunology Research
• Published: 2014;2014:670140
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

It is known that asbestos exposure can cause malignant mesothelioma (MM) and that CD8(+) T cells play a critical role in antitumor immunity. We examined the properties of peripheral blood CD8(+) lymphocytes from asbestos-exposed patients with pleural plaque (PL) and MM. The percentage of CD3(+)CD8(+) cells in PBMCs did not differ among the three groups, although the total numbers of PBMCs of the PL and MM groups were lower than those of the healthy volunteers (HV). The percentage of IFN-γ (+) and CD107a(+) cells in PMA/ionomycin-stimulated CD8(+) lymphocytes did not differ among the three groups. Percentages of perforin(+) cells and CD45RA(-) cells in fresh CD8(+) lymphocytes of PL and MM groups were higher than those of HV. Percentages of granzyme B(+) and perforin(+) cells in PMA/ionomycin-stimulated CD8(+) lymphocytes were higher in PL group compared with HV. The MM group showed a decrease of perforin level in CD8(+) lymphocytes after stimulation compared with patients with PL. These results indicate that MM patients have characteristics of impairment in stimulation-induced cytotoxicity of peripheral blood CD8(+) lymphocytes and that PL and MM patients have a common character of functional alteration in those lymphocytes, namely, an increase in memory cells, possibly related to exposure to asbestos.

In plain English

This laboratory study compared CD8+ lymphocytes, white blood cells that help the immune system kill tumor cells, in blood from three groups of men in Japan: 27 asbestos-exposed patients with pleural plaques, 18 with malignant mesothelioma, and 16 healthy volunteers. The article does not give fiber types or exposure amounts, and some tests used smaller subsets of people. The share of CD3+CD8+ cells did not differ between groups, but the number of these cells per mL of blood was significantly lower in both patient groups. Both patient groups had higher percentages of memory-type (CD45RA-negative) and perforin-containing CD8+ cells than the volunteers. After laboratory stimulation, the plaque group had higher percentages of granzyme B and perforin positive cells than volunteers. The mesothelioma group showed a significantly larger drop in perforin than the other two groups. Interferon-gamma production and degranulation did not differ significantly. The authors concluded that mesothelioma patients showed impaired stimulation-induced cytotoxicity, and that both patient groups shared an increase in memory cells, possibly related to asbestos exposure. They stated they could not draw a conclusion with absolute certainty.

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: Cross-sectional laboratory comparison of blood samples (flow cytometry) from patient groups and healthy volunteers
• Who was studied: Men in Japan: 16 healthy volunteers (mean age 57.2 years), 27 patients with pleural plaques (mean age 66.7 years) and 18 patients with malignant mesothelioma (mean age 67.3 years). Some measurements used subsets: 10 healthy volunteers, 9 plaque patients and 13 mesothelioma patients for CD45RA and CD107a; 16, 16 and 14 for granzyme B and perforin.
• Exposure: Asbestos exposure in the patient groups. No fiber type, product, job or dose is given. In the laboratory, blood cells were stimulated with PMA/ionomycin for 4 hours.
• Main results:
  • The percentage of CD3+CD8+ cells among blood mononuclear cells did not differ among healthy volunteers, plaque patients and mesothelioma patients.
  • The number of CD3+CD8+ cells per mL of blood was significantly lower in the plaque and mesothelioma groups than in healthy volunteers.
  • Memory-type (CD45RA-negative) cells as a percentage of fresh CD8+ lymphocytes were significantly higher in the plaque group (mean 63.4 plus or minus 19.5) and the mesothelioma group (61.7 plus or minus 10.0) than in healthy volunteers (46.5 plus or minus 8.0).
  • The percentage of interferon-gamma positive cells in stimulated CD8+ lymphocytes showed no statistically significant difference among the groups. The mesothelioma group tended to be lower.
  • Perforin positive cells in fresh CD8+ lymphocytes were significantly higher in the plaque group (mean 38.8 plus or minus 26.3) and the mesothelioma group (44.2 plus or minus 24.9) than in healthy volunteers (17.8 plus or minus 14.5).
  • After stimulation, the plaque group had a higher percentage of granzyme B positive CD8+ cells (mean 37.0 plus or minus 26.3) than healthy volunteers (15.2 plus or minus 10.4). It did not differ from the mesothelioma group (29.2 plus or minus 25.3).
  • The change in granzyme B positive cells from fresh to stimulated was significantly higher in the plaque group than in the healthy volunteer or mesothelioma groups.
  • After stimulation, the plaque group, but not the mesothelioma group, had a higher percentage of perforin positive CD8+ cells than healthy volunteers.
  • The change in perforin positive cells from fresh to stimulated was significantly lower in the mesothelioma group than in the plaque and healthy volunteer groups.
  • Degranulation, measured as CD107a positive stimulated CD8+ cells, did not differ statistically among healthy volunteers (mean 7.4 plus or minus 2.8), plaque patients (7.8 plus or minus 3.1) and mesothelioma patients (11.6 plus or minus 5.4).
• The authors' conclusion: The authors concluded that mesothelioma patients show signs of impaired stimulation-induced cytotoxicity of blood CD8+ lymphocytes. They also concluded that plaque and mesothelioma patients share an increase in memory cells, possibly related to asbestos exposure.
• Limitations the authors state:
  • The authors stated they cannot draw a conclusion about the perforin finding in mesothelioma patients with absolute certainty.
  • The authors noted that the impaired CD8+ function in mesothelioma patients might instead be due to immune suppression by tumor cells.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Plaques, Malignant Mesothelioma, Asbestos Exposure.

Related studies

• Decrease in Intracellular Perforin Levels and IFN-γ Production in Human CD8+ T Cell Line following Long-Term Exposure to Asbestos Fibers — N. Kumagai-Takei, Y. Nishimura, et al. (2018)
• The Suppressed Induction of Human Mature Cytotoxic T Lymphocytes Caused by Asbestos Is Not due to Interleukin-2 Insufficiency — N. Kumagai-Takei, Y. Nishimura, et al. (2016)
• Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients — Y. Nishimura, N. Kumagai-Takei, et al. (2015)
• Intratumoral macrophage phenotype and CD8+ T lymphocytes as potential tools to predict local tumor outgrowth at the intervention site in malignant pleural mesothelioma — R. Cornelissen, L.A. Lievense, et al. (2015)
• Effect of asbestos exposure on differentiation and function of cytotoxic T lymphocytes — N. Kumagai-Takei, Y. Nishimura, et al. (2020)
• CD8+ tumor-infiltrating lymphocytes predict favorable prognosis in malignant pleural mesothelioma after resection — N. Yamada, S. Oizumi, et al. (2010)

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