Search for biomarkers of asbestos exposure and asbestos-induced cancers in investigations of the immunological effects of asbestos

Our plain-English summary of Search for biomarkers of asbestos exposure and asbestos-induced cancers in investigations of the immunological effects of asbestos, by H. Matsuzaki, N. Kumagai-Takei, S. Lee, et al (Environmental Health and Preventive Medicine, 2017).

The study

• Authors: H. Matsuzaki, N. Kumagai-Takei, S. Lee, M. Maeda, N. Sada, T. Hatayama, S. Yamamoto, M. Ikeda, K. Yoshitome, Y. Min, Y. Nishimura, T. Otsuki
• Journal: Environmental Health and Preventive Medicine
• Published: 2017;22(1):53
• Type of article: Review
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The immunological effects of asbestos exposure on various lymphocytes such as the regulatory T cell (Treg), responder CD4+ T helper cell (Tresp), CD8+ cytotoxic T lymphocytes (CTL), and natural killer (NK) cells were investigated. Results show that asbestos exposure impairs antitumor immunity through enhancement of regulatory T cell function and volume, reduction of CXCR3 chemokine receptor in responder CD4+ T helper cells, and impairment of the killing activities of CD8+ cytotoxic T lymphocytes (CTL) and NK cells. These findings were used to explore biological markers associated with asbestos exposure and asbestos-induced cancers and suggested the usefulness of serum/plasma IL-10 and TGF-β, surface CXCR3 expression in Tresp, the secreting potential of IFN-γ in Tresp, intracellular perforin level in CTL, and surface expression NKp46 in NK cells. Although other unexplored cytokines in serum/plasma and molecules in these immunological cells, including Th17, should be investigated by experimental procedures in addition to a comprehensive analysis of screening methods, biomarkers based on immunological alterations may be helpful in clinical situations to screen the high-risk population exposed to asbestos and susceptible to asbestos-related cancers such as mesothelioma.

In plain English

This article is a review in which the authors summarized their own laboratory's earlier studies of how asbestos affects human immune cells. They discussed whether these changes could serve as blood markers of asbestos exposure and malignant mesothelioma. The reviewed studies used human cell lines exposed to chrysotile for months (one T cell line also to crocidolite), and blood cells from healthy volunteers and from patients with pleural plaque or malignant mesothelioma. Long-exposed T cell lines made more IL-10 and TGF-β, less CXCR3 and IFN-γ, and showed enhanced regulatory T cell function. Reduced CXCR3 was also seen in blood CD4+ cells from patients, more so in mesothelioma than in pleural plaque. NK cell killing activity was reduced in both patient groups and was significantly correlated with the receptor NKp46. After stimulation, CD8+ cells from mesothelioma patients had lower perforin levels than those from pleural plaque patients. The authors concluded that a combination of such markers might be used for screening. They said further investigation and a standardized method are needed.

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: Review of the authors' own previously published laboratory studies (cell culture experiments and studies of patient blood samples); no new data
• Who was studied: Human cell lines, mainly the T cell line MT-2 and the NK cell line YT-A1, plus peripheral blood cells from healthy volunteers, patients with pleural plaque and patients with malignant mesothelioma studied at Kawasaki Medical School, Japan. The review does not give the numbers of people studied.
• Exposure: Continuous low-dose exposure of cell lines to chrysotile asbestos (for about 1 year for MT-2 and more than 5 months for YT-A1), with MT-2 sublines also made with crocidolite. Chrysotile was also added to a cell culture assay of cytotoxic T cell development. In patients, the exposure was asbestos exposure as shown by pleural plaque or mesothelioma; it was not measured.
• Main results:
  • MT-2 T cell sublines exposed continuously to asbestos showed increased production of IL-10 and TGF-β, reduced surface CXCR3, reduced intracellular IFN-γ, and increased Bcl-2 compared with the original cells
  • Decreased CXCR3 and higher Bcl-2 were also found in peripheral blood CD4+ cells from patients with pleural plaque and mesothelioma; the changes were greater in mesothelioma than in pleural plaque
  • The asbestos-exposed MT-2 sublines showed enhanced regulatory T cell (Treg) suppressive function, reduced FoxO1, increased cyclin D1 and faster cell cycle progression; the authors interpreted this as enhanced Treg function and increased numbers
  • An NK cell line (YT-A1) exposed continuously to chrysotile showed reduced killing of K562 target cells, decreased NKG2D and 2B4 activating receptors, and reduced intracellular perforin
  • Blood NK cells from patients with pleural plaque and mesothelioma showed reduced killing activity, and the surface level of the activating receptor NKp46 was significantly correlated with killing activity
  • When chrysotile was added during the in vitro development of cytotoxic T cells from healthy volunteers' blood cells, proliferation of CD8+ cells, their differentiation and IFN-γ production were impaired. Adding IL-2 restored killing activity but not CD8+ cell numbers.
  • In patient blood, total PBMC numbers were lower in pleural plaque and mesothelioma than in healthy volunteers. The percentage of CD8+ cells did not differ between the three groups.
  • After stimulation, the percentage of granzyme B+ and perforin+ CD8+ cells was higher in the pleural plaque group than in healthy volunteers. The mesothelioma group showed lower perforin in CD8+ cells than the pleural plaque group.
• The authors' conclusion: The authors concluded that these immune changes suggest biomarker candidates for detecting asbestos exposure and mesothelioma. Candidates include serum or plasma IL-10 and TGF-β, CXCR3 and IFN-γ in CD4+ cells, perforin in CD8+ cells, and NKp46 in NK cells. They proposed using these markers in combination, since a single marker may not be enough. They stated that immunological markers are better than radiological screening for cost and procedure, and possibly for accuracy.
• Limitations the authors state:
  • The authors stated that a single marker may not be able to detect past or present asbestos exposure or mesothelioma
  • The authors stated that a standardized method for processing blood samples would be needed before such markers could be used
  • The authors stated that other cytokines and immune cell types, including Th17 cells, have not yet been investigated and that additional investigations are necessary

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Asbestos Exposure, Cytokine, Mesothelioma.

Related studies

• Environmental factors and human health: fibrous and particulate substance-induced immunological disorders and construction of a health-promoting living environment — T. Otsuki, H. Matsuzaki, et al. (2016)
• Accelerated cell cycle progression of human regulatory T cell-like cell line caused by continuous exposure to asbestos fibers — S. Lee, H. Matsuzaki, et al. (2017)
• Aberrant expression of FoxP3 in a human T cell line possessing regulatory T cell‑like function and exposed continuously to asbestos fibers — M. Maeda, H. Matsuzaki, et al. (2018)
• Altered functions of alveolar macrophages and NK cells involved in asbestos-related diseases — Y. Nishimura, M. Maeda, et al. (2013)
• 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)
• Enhancement of regulatory T cell-like suppressive function in MT-2 by long-term and low-dose exposure to asbestos — C. Ying, M. Maeda, et al. (2015)

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