Immunological changes in mesothelioma patients and their experimental detection

Our plain-English summary of Immunological changes in mesothelioma patients and their experimental detection, by M. Maeda, Y. Miura, Y. Nishimura, et al (Clinical Medicine. Circulatory, Respiratory and Pulmonary Medicine, 2008).

The study

• Authors: M. Maeda, Y. Miura, Y. Nishimura, S. Murakami, H. Hayashi, N. Kumagai, T. Hatayama, M. Katoh, N. Miyahara, S. Yamamoto, K. Fukuoka, T. Kishimoto, T. Nakano, T. Otsuki
• Journal: Clinical Medicine. Circulatory, Respiratory and Pulmonary Medicine
• Published: 2008;2:11-7
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

It is common knowledge that asbestos exposure causes asbestos-related diseases such as asbestosis, lung cancer and malignant mesothelioma (MM) not only in people who have handled asbestos in the work environment, but also in residents living near factories that handle asbestos. These facts have been an enormous medical and social problem in Japan since the summer of 2005. We focused on the immunological effects of asbestos and silica on the human immune system. In this brief review, we present immunological changes in patients with MM and outline their experimental detection. For example, there is over-expression of bcl-2 in CD4+ peripheral T-cells, high plasma concentrations of interleukin (IL)-10 and transforming growth factor (TGF)-ß, and multiple over-representation of T cell receptor (TcR)-Vß in peripheral CD3+ T-cells found in MM patients. We also detail an experimental long-term exposure T-cell model. Analysis of the immunological effects of asbestos may help our understanding of the biological effects of asbestos.

In plain English

This brief review by a Japanese research group summarized the group's own earlier clinical and laboratory findings on how asbestos may alter T cells of the immune system in people with malignant mesothelioma (MM). Peripheral CD4+ T cells from MM patients had significantly higher expression of the gene bcl-2 than those of healthy volunteers, and plasma levels of the anti-inflammatory cytokines IL-10 and TGF-ß were significantly higher in MM patients. In the laboratory, the group developed a T-cell line that, after low-dose, long-term chrysotile exposure, resisted asbestos-induced cell death; these cells showed more bcl-2 and secreted more IL-10 and TGF-ß than the original cells. Blood from 12 MM patients and 9 asbestosis patients, compared with 6 healthy volunteers, showed over-expression of various T-cell receptor Vß types, as did the resistant cells. The authors concluded that asbestos affects immune cells and that these effects may be associated with the development of malignant tumors. They noted the data came from a limited number of patients.

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: Brief review of the authors' own earlier clinical findings in patients and laboratory cell-line experiments
• Who was studied: Patients with malignant mesothelioma and healthy volunteers in Japan. For the T-cell receptor analysis, blood came from 6 healthy volunteers (mean age 38.0, 1 man and 5 women), 9 asbestosis patients (mean age 74.4, all men) and 12 MM patients (mean age 58.7, 9 men and 3 women). The numbers of patients in the bcl-2, cytokine and factor analyses are not stated. Laboratory work used MT-2, a human T-cell line.
• Exposure: Laboratory experiments mainly used chrysotile, including short-term high-dose and long-term low-dose exposure of a T-cell line. Patients' past asbestos exposure was recorded as present, unknown or none in the factor analysis.
• Main results:
  • Peripheral CD4+ T cells from MM patients showed significantly higher bcl-2 expression than those of healthy volunteers (a finding reported in the authors' earlier paper, Miura et al. 2006).
  • In the chrysotile-induced apoptosis-resistant cell line (MT-2Rst), the authors found enhanced bcl-2 expression, excessive IL-10 secretion and expression, and STAT3 activation.
  • In a factor analysis of MM patients, four measures formed one factor: higher bcl-2 expression in CD4+ T cells (0.59009), past asbestos exposure (0.55496), lower platelet count (-0.76064) and lower serum CRP (-0.79789). The factor's contribution rate was 19.18%.
  • Plasma concentrations of IL-10 and TGF-ß were significantly higher in MM patients than in healthy volunteers.
  • MT-2Rst cells secreted significantly more TGF-ß than the original MT-2 cells, and their IL-10 concentration in culture was also higher.
  • Various T-cell receptor Vß types were over-expressed in MM and asbestosis patients compared with healthy volunteers (above the healthy-volunteer mean plus 2 standard deviations). Vß 1, 4 and 9 were strongly over-expressed in many patients.
  • The asbestos-resistant MT-2Rst cells also over-expressed various T-cell receptor Vß types.
• The authors' conclusion: The authors concluded that asbestos affects immune cells and that these effects may be associated with the development of complications such as malignant tumors in asbestos-exposed patients. They suggested that the elevated TGF-ß and IL-10 in MM patients come not only from tumor cells but also from immune cells. They also suggested that multiple T-cell receptor Vß over-expression may be a candidate marker of previous asbestos exposure.
• Limitations the authors state:
  • The T-cell receptor data came from a limited number of patients.
  • It was not determined whether patients with other cancers show the same bcl-2 over-expression.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Asbestos Exposure, Lung Cancer, Malignant Mesothelioma.

Related studies

• Immunological alterations found in mesothelioma patients and supporting experimental evidence — Y. Miura, Y. Nishimura, et al. (2008)
• Cytokine alteration and speculated immunological pathophysiology in silicosis and asbestos-related diseases — S. Murakami, Y. Nishimura, et al. (2009)
• Search for biomarkers of asbestos exposure and asbestos-induced cancers in investigations of the immunological effects of asbestos — H. Matsuzaki, N. Kumagai-Takei, et al. (2017)
• Dysregulation of the immune system caused by silica and asbestos — M. Maeda, Y. Nishimura, et al. (2010)
• 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)
• Reduction of CXC chemokine receptor 3 in an in vitro model of continuous exposure to asbestos in a human T-cell line, MT-2 — M. Maeda, Y. Nishimura, et al. (2011)

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