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Epigenetics Used to Improve Immunotherapy for Mesothelioma

Published: January 21, 2022

Researchers are looking into changing mesothelioma cells to make them more susceptible to immunotherapy. Mesothelioma is a hard cancer to treat, so new approaches need to be developed to try to lengthen and improve mesothelioma patients’ lives. Immunotherapy can work well for some, but for others it does very little, so researchers need to find ways to augment and improve mesothelioma treatments. If they do this, more patients can possibly benefit from the innovative immune system-based treatments. Researchers have possibly found a way to make cells more susceptible to immunotherapy. They think that if they alter the gene expression of mesothelioma cells, the cells will respond more to immunotherapy treatments.

Immunotherapy is a treatment that utilizes the immune system to fight cancer. There are many different types of immunotherapy. Some bring immune system cells to the cancer and some make cancer cells sensitive to the immune system. It can be hard to make these treatments work for mesothelioma though because mesothelioma cells can modulate their response to immunotherapy. They do this by releasing proteins that are harmful to immune system cells. Doctors want to make the area surrounding mesothelioma more accommodating to immunotherapy drugs because if they do, they believe they can make mesothelioma more susceptible to immunotherapy treatments.

Certain expressed genes control how cells respond to immunotherapy. Mesothelioma cells are able to control gene activity through epigenetics, which is the changing of gene activity without changing DNA. Drugs are also able to create epigenetic changes, and this study is utilizing these drugs to change the mesothelioma tumor microenvironment (area surrounding mesothelioma cells). The doctors wanted to see if any drugs made mesothelioma cells responsive to immunotherapy. They tested multiple drugs and guadecitabine had the best impact. When the drug was administered, it activated genes relating to immune functions in sarcomatoid mesothelioma.

Other epigenetic drugs were tested on different types of mesothelioma. After the tests, the doctors were able to conclude that epigenetic drugs can potentially increase mesothelioma responsiveness to immunotherapy treatments. They want to see other epigenetic drugs tested with multiple types of mesothelioma to see what levels of response occur with different combinations. The researchers believe that multiple therapies can be developed for the treatment of mesothelioma that involve epigenetic drugs and immunotherapy. This shows why mesothelioma studies are so important. Researchers were able to find a possible new treatment that could help mesothelioma patients live longer lives.

Maria Fortunata Lofiego et al., “Epigenetic Immune Remodeling of Mesothelioma Cells: A New Strategy to Improve the Efficacy of Immunotherapy” Epigenomes (December 14, 2021). [Link]
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