Exposure to airborne asbestos fibers is the leading cause of malignant mesothelioma worldwide, but scientists are still unclear on exactly what makes healthy mesothelial cells in the membranes around organs give rise to mesothelioma tumors.
Now, scientists at Kawasaki Medical School and Okayama University in Okayama say continuous exposure to asbestos appears to have an impact on the life cycle of regulatory T-cells, the cells that help to fight off tumors before they start.
Testing the Role of T-cells in Malignant Mesothelioma
To test their T-cell theory, researchers took blood samples from healthy people as well as from those with asbestos-related conditions such as pleural plaques and pleural mesothelioma.
From these blood samples, the team extracted immune cells and tested how healthy they were. They found a decrease in the activity of “natural killer cells”, reduced production of new T-cells, and other changes that could support mesothelioma development.
Asbestos Disrupts Cell Cycle
When the researchers took the experiment a step further and exposed isolated MT-2 human polyclonal T-cells to asbestos fibers directly, they showed a “remarkable” reduction in FoxO1, a transcription factor which plays a role in regulating the life cycles of cells, including immune system cells.
In addition, the cells exposed continuously to asbestos overexpressed cyclin D1, a cell cycle regulator that has been linked to the development and progression of cancers such as malignant mesothelioma. These cells also showed an increase in the DNA-replicating part of their life cycle (S phase).
“The overall findings indicate that antitumor immunity in asbestos-exposed individuals may be reduced…through changes in the function and volume of regulatory T-cells,” writes study author Dr. Suni Lee in a report summary in the International Journal of Oncology.
Multiple Causes of Mesothelioma
As with most cancers, the mechanisms that give rise to mesothelioma are varied and complex.
In addition to asbestos-related changes in immunity, mesothelioma has also been linked to asbestos-related inflammation at the cellular level and to certain genes which appear to predispose people to the disease. In particular, people with changes to their BAP1 gene, are more likely to develop mesothelioma if exposed to asbestos.
Mesothelioma is one of the world’s rarest cancers, affecting fewer than 3,000 people in the US each year. The workplace is the most common site for asbestos exposure.
Lee, S, et al, “accelerated cell cycle progression of human regulatory T cell-like cell line caused by continuous exposure to asbestos fibers”, November 2016, International Journal of Oncology, Epub ahead of print