Not just from depression
Antidepressants – to help cancer immunotherapy
Cancer immunotherapy is aimed at activating the body's own antitumor defense, but the effectiveness of this relatively new treatment method is still low. Recently, using the example of laboratory mice, it was shown that it can be increased with the help of already known antidepressants.
Article by Wang et al. Targeting monoamine oxidase A for T cell–based cancer immunotherapy is published in the journal Science Immunology.
The fight against cancer cells is one of the direct tasks of the immune system. And when the development of cancer immunotherapy methods began at the end of the last century, great hopes were pinned on them, which, unfortunately, were not fully justified.
What is the problem? Tumor cells are able to "slow down" the work of immune cells (T-lymphocytes) by binding to special molecules on their surface – PD-1 receptors. In this way, they avoid attacks by T-lymphocytes.
However, if these receptors are blocked, then the immune cells will destroy the malignant ones. This is exactly what immunotherapeutic drugs, which are monoclonal antibodies against PD-1 receptors, do. In some patients, such treatment does cause remission for many years, but for many it practically does not help.
In search of a solution to this problem, American scientists studied in detail the work of genes in T-lymphocytes in mice with melanoma, and unexpectedly found an unusually high activity of the MAO-A gene in them.
This gene is quite well known, but not in connection with oncological diseases. MAO-A is also called the "warrior gene", since the low level of its activity in some men is accompanied by aggressive behavior. But a high level is associated with the development of depression. MAO-A encodes an enzyme that is found in nerve endings and breaks down neurotransmitters and hormones, including serotonin, associated with mood and anxiety levels. Therefore, back in the middle of the last century, low–molecular-weight inhibitors of this enzyme were created for the treatment of neurological disorders. However, today they are used infrequently, as they have many side effects.
Using IMAO in mutant mice with reduced activity of the "warrior gene", the researchers found that their cancer tissues grow more slowly, and T-lymphocytes produce more molecules that are toxic to the tumor. In normal mice with implanted melanoma or colon cancer cells, IMAO also slowed the growth of tumors. Moreover, the combination of these inhibitors with an immunotherapeutic drug against PD-1 worked better than each of them separately.
A search in databases showed that cancer patients with high activity of the MAO-A gene had fewer T-lymphocytes in the tumor, and they had a fatal outcome earlier. According to scientists, the whole point is that T-lymphocytes produce their own serotonin, which helps them actively fight the tumor, and the MAO-A gene promotes the breakdown of this hormone, so that its activation plays into the hands of malignant cells.
Thus, low-molecular "assistants" may soon appear in the arsenal of cancer immunotherapy, increasing its effectiveness. In addition, the addition of IMAO to cancer treatment regimens will simultaneously contribute to the normalization of the psychological state of such patients.
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