Immunotherapy for mesothelioma is an emerging treatment that uses the body’s immune system to destroy cancer cells, shrink tumors, and treat symptoms. There are various ways to use the immune system to fight cancer, including strengthening the body’s immune system and adding synthetic components.[1] Immunotherapy has helped some patients live longer, but more research is needed to determine if it can cure mesothelioma or any other cancer.[2]
How the Immune System Works
The immune system protects the body from pathogens like viruses and bacteria. It fights infections and prevents disease. This system also recycles and removes dead and damaged cells.
From the moment of birth, the immune system recognizes foreign agents in the body; however, the immune system also develops as a person is exposed to pathogens.[3]
The immune system includes several types of immune compounds and cells:[3][4]
- B and T lymphocytes, or B and T cells, are white blood cells. B cells make antibodies.
- T cells produce compounds called cytokines that clean up dead and diseased cells.
- Antibodies are proteins that recognize antigens, which are compounds on the surfaces of infectious agents. Antibodies signal the immune system to attack a pathogen by recognizing antigens.
- Macrophages are large immune system cells that consume dead cells and cellular debris.
What Is Immunotherapy?
Immunotherapy is a cancer treatment strategy that uses the body’s immune system to fight cancer cells. There are two main ways to do this:[1]
- The first method stimulates the immune system to make it work harder or to target cancer cells specifically.
- The second strategy adds immune system components to instigate an attack on cancer cells. The treatment may be specific, encouraging immune cells to target one type of cancer cell or general, boosting the actions of the immune system overall.
Monoclonal Antibodies
The immune system produces proteins called antibodies that circulate in the body, attaching to antigens wherever they encounter them. Once attached to the antigens, the antibodies recruit other cells to fight the invader.
Researchers can create antibodies in the lab designed specifically to target an antigen. If cancer researchers know what antigen is present in the cancer, they can design an antibody to trigger the immune system to attack the cancer cells. Antibodies created in this way are known as monoclonal antibodies.[1]
Monoclonal antibodies work better for some types of cancer than others. Identifying an antigen is important, but this is not always easy.
For mesothelioma, a possible targeted antigen is mesothelin. Using monoclonal antibodies is not a cure for mesothelioma; however, they can be used in conjunction with other treatments, like surgery. The strategy can be more effective for some patients than others.[5]
Cancer Vaccines
Vaccines are manipulated pathogens, like viruses, administered to prevent illness. For instance, millions of people get the flu vaccine each year. The flu vaccine uses inactivated flu viruses to stimulate the immune system to recognize and attack the active flu virus to prevent infection.
Cancer vaccines work similarly. They are used to stimulate the immune system to attack cancer cells to actively treat the cancer or prevent the regrowth of tumors after remission.[6]
Immune Checkpoint Inhibitors
The immune system should be able to distinguish between healthy cells and pathogens. To do this, certain molecules on immune cells must be activated to attack pathogens.
Cancer cells can develop molecular strategies to get around these checkpoints, effectively avoiding attacks from immune system cells. One emerging immunotherapy strategy targets checkpoints with specially designed drugs.[7]
Checkpoint inhibitors currently used for mesothelioma treatment are pembrolizumab (Keytruda) with nivolumab (Opdivo) and ipilimumab (Yervoy). The combination and single drug target different T cell proteins.[8]
Passive Immunotherapy
A passive approach to immunotherapy uses strategies to boost the immune system without specificity. This approach is often called non-specific immunotherapy. These strategies may be used alone, with other types of immunotherapy, or with other types of cancer treatments.
One passive strategy is to inject the body with cytokines and immune system proteins that promote the growth and development of immune cells. There are also synthetic drugs that boost the immune system, although how they work is not fully understood.[9]
A type of bacterium can also boost the immune response. BCG, or Bacille Calmette-Guérin, is commonly used in bladder and skin cancers. A solution of the bacteria is injected into the bladder, attracting immune cells which then attack cancer.
Studies from the 1970s to 1980s looked at the possible effectiveness in treating other cancers. It is not currently used to treat mesothelioma unless as part of a clinical trial. BCG does not cause infections in people, although it does stimulate inflammatory symptoms. These are similar to flu symptoms and are relatively mild.[10]
BCG has been tested in mesothelioma patients. In one study, the treatment helped prevent pleural effusions, the buildup of fluid in the chest cavity.
Another study involved mesothelioma patients who had undergone a thoracotomy. These patients received regular injections of BCG after the surgery. Results of the study showed this treatment could significantly reduce symptoms.[10]
The Challenges of Treating Patients with Autoimmune Disorders
Immunotherapy has enormous potential to help people living with cancer, but there is one group of patients for which this type of treatment presents a problem. Autoimmune diseases are illnesses caused by the immune system attacking healthy cells in the body.[11]
Examples include rheumatoid arthritis, in which the immune system attacks the joints, and psoriasis, which affects the skin. These diseases can affect many different parts of the body and cause uncomfortable symptoms, some severe.[11]
When someone has an autoimmune disorder, their immune system is unable to recognize the difference between antigens produced by harmful cells (bacteria, viruses, cancer cells) and healthy cells. Why this happens is not well understood, but a typical treatment is a medication that suppresses the immune system.[12]
This can relieve symptoms and slow the progress of healthy tissue damage, but it also hampers the immune system’s ability to fight cancer cells.[13]
The treatment that helps relieve autoimmune disorders counteracts the purpose of immunotherapy for cancer, which is to boost the immune system. An immunotherapy drug may be useful for a particular type of cancer, but the patient with an autoimmune disease may not be able to tolerate it. It may worsen the progression of that disease.[13]
The challenge of oncologists working with patients who have both cancer and an autoimmune disorder is to balance both. They have to try to find the right level of immune-suppressing drugs that keep the disorder in check while also determining how much of a checkpoint inhibitor the patient can tolerate and that is effective in fighting cancer.[13]
Another issue is the fact that inflammation caused by autoimmune disorders can trigger cancer. For instance, someone with Crohn’s disease, which causes inflammation in the bowels, has an elevated risk of developing colon cancer. Treating an autoimmune patient with immunotherapy is a matter of weighing risks against benefits and requires expert guidance.[13]
Immunotherapy for Mesothelioma
Using immunotherapy to treat mesothelioma has been tricky. For instance, targeting antigens is difficult because mesothelioma cells seem to produce few antigens.
Mesothelin is one of the few recognized, but it is not produced in all cases of mesothelioma. BCG showed some success in early studies but has not become a regular treatment for mesothelioma.
Immunotherapy continues to be a promising line of treatment. Continuing research should lead to developments that help more patients with cancer, specifically those with mesothelioma.
Boosting the immune system seems to have some impact on patient outcomes; however, to have a positive effect, immunotherapy often must be used with other treatments. As research continues, more advances should be found, giving patients hope and comfort as they fight mesothelioma.
