Asbestos induces reduction of tumor immunity

Our plain-English summary of Asbestos induces reduction of tumor immunity, by N. Kumagai-Takei, M. Maeda, Y. Chen, et al (Clinical & Developmental Immunology, 2011).

The study

• Authors: N. Kumagai-Takei, M. Maeda, Y. Chen, H. Matsuzaki, S. Lee, Y. Nishimura, J. Hiratsuka, T. Otsuki
• Journal: Clinical & Developmental Immunology
• Published: 2011;2011:481439
• Type of article: Review
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos-related cancers such as malignant mesothelioma and lung cancer are an important issue in the world. There are many conflicts concerning economical considerations and medical evidence for these cancers and much confusion regarding details of the pathological mechanisms of asbestos-induced cancers. For example, there is uncertainty concerning the degree of danger of the iron-absent chrysotile compared with iron-containing crocidolite and amosite. However, regarding bad prognosis of mesothelioma, medical approaches to ensure the recognition of the biological effects of asbestos and the pathological mechanisms of asbestos-induced carcinogenesis, as well as clinical trials to detect the early stage of mesothelioma, should result in better preventions and the cure of these malignancies. We have been investigating the immunological effects of asbestos in relation to the reduction of tumor immunity. In this paper, cellular and molecular approaches to clarify the immunological effects of asbestos are described, and all the findings indicate that the reduction of tumor immunity is caused by asbestos exposure and involvement in asbestos-induced cancers. These investigations may not only allow the clear recognition of the biological effects of asbestos, but also present a novel procedure for early detection of previous asbestos exposure and the presence of mesothelioma as well as the chemoprevention of asbestos-related cancers.

In plain English

This was a review in which the authors summarized their own group's earlier laboratory research on how asbestos affects immune cells that help fight tumors. Most of this work used chrysotile asbestos. In a human T-cell line (MT-2), brief high-dose chrysotile exposure caused cell death. More than eight months of low-dose exposure produced sublines that resisted this cell death. These sublines also had lower levels of CXCR3, a receptor linked to anti-tumor activity, and of interferon-gamma. CD4+ T cells from healthy donors, grown with chrysotile, showed a CXCR3 decrease in four of six donors. CD4+ T cells from patients with pleural plaque or malignant mesothelioma showed reduced CXCR3 compared with healthy donors, and interferon-gamma was reduced only in the mesothelioma patients. Natural killer cells exposed to chrysotile had lower levels of activating receptors. Natural killer cells from mesothelioma patients killed target cells less well and carried less of a receptor called NKp46. The authors concluded that people exposed to asbestos have reduced tumor immunity, making them sensitive to cancer development. They noted that other fiber types still needed study.

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 laboratory studies (cell-line experiments, experiments on blood cells from healthy donors exposed in the laboratory, and analyses of blood cells from patients)
• Who was studied: A human T-cell line (MT-2), a human natural killer cell line (YT-A1), immune cells from healthy donors (CD4+ T cells from six donors in one experiment), and blood cells from patients with pleural plaque or malignant mesothelioma in Japan. Patient numbers were not given.
• Exposure: Chrysotile asbestos (chrysotile A and chrysotile B) in laboratory cultures. Brief high-dose exposure was 25 to 50 micrograms per mL. Continuous low-dose exposure was 5 or 10 micrograms per mL for more than eight months in the MT-2 cell line. Patients had been exposed to asbestos and had pleural plaque or mesothelioma.
• Main results:
  • In MT-2 cells, brief high-dose chrysotile exposure led to production of reactive oxygen species and then to programmed cell death (apoptosis).
  • Continuous low-dose exposure produced MT-2 sublines that resisted chrysotile-induced apoptosis. These sublines showed increased IL-10, STAT3 activation with BCL-2 overexpression, and upregulated TGF-beta.
  • All six continuously exposed MT-2 sublines had reduced CXCR3 on their surface and at the mRNA level, with reduced interferon-gamma.
  • In CD4+ T cells from healthy donors cultured with chrysotile, four of six donors showed a decrease in CXCR3 to various degrees. The authors noted that the significant reduction at 10 micrograms per mL for 28 days seemed to depend on one donor.
  • CD4+ T cells from asbestos-exposed patients showed reduced CXCR3. CXCR3 was lower in mesothelioma patients than in pleural plaque patients, but this difference was not statistically significant.
  • When stimulated, CD4+ T cells showed reduced interferon-gamma only in mesothelioma patients, not in pleural plaque patients.
  • Natural killer cells from mesothelioma patients showed reduced killing function and lower NKp46 compared with those from healthy donors. The YT-A1 natural killer cell line exposed continuously to chrysotile showed reduced NKG2D and 2B4.
  • Preliminary findings in the MT-2 model suggested that asbestos may enhance regulatory T cell (Treg) function.
• The authors' conclusion: The authors concluded that people exposed to asbestos have reduced tumor immunity, making them sensitive to cancer development. They suggested that changes in immune cells might help detect past asbestos exposure and cancer.
• Limitations the authors state:
  • The authors mainly studied chrysotile and stated that differences and similarities between fiber types should also be investigated.
  • The reduction of CXCR3 in healthy donors' CD4+ T cells seemed to depend on one donor whose levels dropped sharply.
  • Culture of healthy donors' CD4+ T cells was limited to around four weeks.
  • Work on CD8+ cytotoxic T cells had only just started.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Lung Cancer, Chrysotile, Crocidolite, Amosite, Prognosis, Mesothelioma, Carcinogenesis.

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