A New Way to Fight Mesothelioma: How a Combination of Radiation, Chemotherapy and Immunotherapy Can Boost the Immune System to Kill Cancer Cells
A New Way to Fight Mesothelioma: How a Combination of Radiation, Chemotherapy and Immunotherapy Can Boost the Immune System to Kill Cancer Cells
Mesothelioma is a rare and aggressive type of cancer that affects the lining of the lungs and chest cavity. Mesothelioma is mainly caused by exposure to asbestos, a mineral fiber that was widely used in construction and industry until its ban in many countries. Mesothelioma has a poor prognosis, with a median survival of less than one year after diagnosis.
Mesothelioma is difficult to treat, as it has no specific symptoms and is resistant to most conventional therapies, such as surgery, chemotherapy and radiation. Therefore, there is an urgent need for new and effective treatments that can target and kill mesothelioma cells.
This article is a summary of a new way to fight mesothelioma that combines radiation, chemotherapy and immunotherapy to maximize antitumor immune responses1. The combination therapy uses low doses of radiation and chemotherapy to damage mesothelioma cells and make them more visible to the immune system. The combination therapy also uses immunotherapy to stimulate the immune system to recognize and attack mesothelioma cells.
The article was published in the journal Science Translational Medicine in 2021 by a team of researchers from Australia and Canada.
What is radiation therapy?
Radiation therapy is a treatment that uses high-energy rays or particles to kill cancer cells or stop them from growing. Radiation therapy can be delivered externally (by a machine that aims radiation at the tumor) or internally (by placing radioactive materials near or inside the tumor).
Radiation therapy can damage both cancer cells and normal cells, but normal cells can usually repair themselves better than cancer cells. Radiation therapy can also cause side effects, such as fatigue, skin irritation, nausea or hair loss.
What is chemotherapy?
Chemotherapy is a treatment that uses drugs to kill cancer cells or stop them from growing. Chemotherapy can be given orally (by mouth), intravenously (by injection into a vein) or intrapleurally (by injection into the chest cavity).
Chemotherapy can affect both cancer cells and normal cells, but normal cells can usually recover faster than cancer cells. Chemotherapy can also cause side effects, such as nausea, vomiting, hair loss, infection or bleeding.
What is immunotherapy?
Immunotherapy is a treatment that uses substances that stimulate or enhance the immune system to fight cancer. Immunotherapy can be given as vaccines (that introduce antigens or substances that trigger an immune response), antibodies (that bind to specific targets on cancer cells or immune cells), cytokines (that modulate the activity of immune cells) or checkpoint inhibitors (that block signals that prevent the immune system from attacking cancer cells).
Immunotherapy can have different effects on different people, depending on their genetic makeup and tumor characteristics. Immunotherapy can also cause side effects, such as rash, fever, fatigue or inflammation.
What is the combination therapy?
The combination therapy is a triple-modality therapy that combines low doses of radiation therapy, chemotherapy and immunotherapy to maximize antitumor immune responses in mesothelioma. The combination therapy uses the following components:
- Radiation therapy: The combination therapy uses low doses of external beam radiation therapy (EBRT) to deliver radiation to the tumor site. EBRT damages mesothelioma cells and causes them to release antigens (substances that trigger an immune response) and danger signals (substances that alert the immune system of tissue damage). EBRT also reduces the number of regulatory T cells (Tregs), which are immune cells that suppress the immune response.
- Chemotherapy: The combination therapy uses low doses of cisplatin and pemetrexed, which are chemotherapy drugs that are commonly used to treat mesothelioma. Cisplatin and pemetrexed damage mesothelioma cells and cause them to release more antigens and danger signals. Cisplatin and pemetrexed also reduce the number of myeloid-derived suppressor cells (MDSCs), which are immune cells that inhibit the immune response.
- Immunotherapy: The combination therapy uses a checkpoint inhibitor called anti-PD-1, which is an antibody that blocks the interaction between PD-1 (a receptor on immune cells) and PD-L1 (a ligand on cancer cells or immune cells). PD-1 and PD-L1 interaction prevents the immune system from attacking cancer cells. Anti-PD-1 releases the brake on the immune system and allows it to recognize and attack mesothelioma cells.
What were the main results of the study?
The study tested the combination therapy in a mouse model of mesothelioma. The study used mice that were genetically engineered to develop mesothelioma tumors in their chest cavity. The study compared the effects of the combination therapy with those of single or dual therapies. The main results of the study were:
- The combination therapy was more effective than single or dual therapies: The combination therapy was more effective than single or dual therapies in reducing tumor growth and prolonging survival in mice with mesothelioma tumors. The combination therapy also prevented tumor recurrence and metastasis (the spread of cancer cells to other parts of the body) in mice that had their tumors surgically removed.
- The combination therapy enhanced antitumor immune responses: The combination therapy enhanced antitumor immune responses in mice with mesothelioma tumors. The combination therapy increased the number and activity of CD8+ T cells, which are immune cells that can directly kill cancer cells. The combination therapy also increased the number and activity of natural killer (NK) cells, which are immune cells that can recognize and kill cancer cells. The combination therapy also increased the expression of genes that are involved in immune activation and inflammation, such as IFNγ, TNFα and IL-6.
- The combination therapy induced immunological memory: The combination therapy induced immunological memory in mice with mesothelioma tumors. Immunological memory is the ability of the immune system to remember and respond to previous antigens or infections. Immunological memory can provide long-term protection against cancer recurrence or metastasis. The combination therapy induced immunological memory by increasing the number and activity of memory T cells, which are immune cells that can quickly respond to antigens that they have encountered before.
What are the implications of the study?
The study provides a new way to fight mesothelioma that combines low doses of radiation therapy, chemotherapy and immunotherapy to maximize antitumor immune responses. The combination therapy uses radiation and chemotherapy to damage mesothelioma cells and make them more visible to the immune system. The combination therapy also uses immunotherapy to stimulate the immune system to recognize and attack mesothelioma cells.
The study suggests that the combination therapy could be a promising strategy to treat mesothelioma, as it could reduce tumor growth and prolong survival in patients with mesothelioma. The study also suggests that the combination therapy could prevent tumor recurrence and metastasis in patients who undergo surgery for mesothelioma. The study also suggests that the combination therapy could induce immunological memory in patients with mesothelioma, which could provide long-term protection against cancer relapse.
The study was conducted by a team of researchers from Australia and Canada. The study was published in the journal Science Translational Medicine in 2021. The title and authors of the original article are:
Triple-modality therapy maximizes antitumor immune responses in a mouse model of mesothelioma by Steven Kao, Yuen Yee Cheng, Sumedha Gattani, Trishe Leong, Michaela Kirschner, Brian C. McCaughan, Nico van Zandwijk & Glen Reid.
1: Kao S, Cheng YY, Gattani S, et al. Triple-modality therapy maximizes antitumor immune responses in a mouse model of mesothelioma. Sci Transl Med. 2021;13(607):eabd9882. doi:10.1126/scitranslmed.abd9882