In a study presented today at the American Association for Cancer Research Annual Meeting 2024, researchers at Fox Chase Cancer Center showed that mice with a BAP1 germline mutation, after exposure to small levels of asbestos, had a greater chance of developing malignant mesothelioma. The study is being published in Cancer Research Communications, a journal in the American Journal for Cancer Research. BAP1 mutations are inherited conditions that increase the likelihood of different cancers that occur commonly in the abdomen, skin, eyes, kidneys, and tissue lining the chest. People with BAP1 mutations are especially at risk of developing malignant mesothelioma, which is a cancer of the mesothelium, a thin membrane that lines different areas of the body.
It is often debated whether chrysotile asbestos can cause mesothelioma or lung cancer. This study is important because chrysotile asbestos makes up 95 percent of the asbestos used commercially. Some people say it causes disease while others say it only causes disease because it is contaminated with another form of asbestos called crocidolite. This led to researchers testing low levels of chrysotile and crocidolite to see if it caused cancer in normal mice or mice with the inherited BAP1 gene mutation.
Over a four-year period, mice with a genetic mutation of the BAP1 gene and mice with a normal genome were examined to see if the BAP1 gene mutation mice developed mesothelioma more often. To determine the effects of asbestos, low levels of the substance were injected into the abdomens of mice. The mice with the BAP1 mutation developed mesothelioma more often than mice without the mutation. It did not matter how much asbestos a mouse was exposed to. This shows that BAP1 mutation carriers are very susceptible to the carcinogenic effects of even minimal amounts of asbestos, including crocidolite and chrysotile.
Inflammation from asbestos, especially chrysotile, creates an immunosuppressive tumor microenvironment in BAP1-mutant mice, which allows conditions where malignant mesothelioma cells can evade immune surveillance. This could mean that immunotherapies that target these pathways in BAP1 mutation carriers who develop mesothelioma could be an effective treatment option in the future. The study was presented at the AACR Annual Meeting 2024, which was held from April 5-10 in San Diego. The full study can be found online. It is titled “Low Exposures to Amphibole or Serpentine Asbestos in Germline Bap1-Mutant Mice Induce Mesothelioma Characterized by an Immunosuppressive Tumor Microenvironment.”
