Asbestos induces reduction of tumor immunity

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.

Figure 1

Schematic model showing mechanisms of asbestos-induced carcinogenesis and genomic/epigenetic changes found in mesothelioma cells and the relationship of the immunological effects of asbestos in regard to reduced tumor immunity.

Figure 2

Summarized findings of cellular and molecular events caused by high-dose and transient exposure (left side) and lowdose and continuous exposure (CB1: one of the sublines established) (right side) to chrysotile asbestos using an HTLV-1 immortalized human polyclonal T cell line, MT-2.

Figure 3

Schematic representation of asbestos-induced reduction of expression of a chemokine receptor, CXCR3, and expression and production of IFN-γ using the MT-2 cell line model (Org; MT-2 original cell line, and Rst: sublines exposed continuously to a low-dose of chrysotile), an ex vivo exposure model using freshly isolated CD4+ T cells from healthy donors (HD), as well as analyses of freshly isolated CD4+ T cells from healthy donors and patients with pleural plaque (PP) and malignant mesothelioma (MM).

Figure 4

Schematic representation of findings showing asbestos-induced reduction of tumor immunity on CD4+ T cells, CD4+25+FoxP3+ regulatory T cells (Treg), T helper (Th)17, CD8+ cytotoxic T cells (CTL), natural killer (NK) cells, monocyte-macrophage, dendritic cells (DC), and natural killer T cells (NKT).