The drug commonly used as an antidepressant helps fight cancer in mice


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A class of drugs called monoamine oxidase inhibitors are usually prescribed to treat depression; the drugs work by increasing levels of serotonin, the brain’s “happiness hormone.”

A new study by UCLA researchers suggests that those drugs, commonly known as MAOIs, may have another health benefit: helping attack . His findings are reported in two papers published in journals Scientific immunology i Communications on Nature.

“MAOIs had not been linked to the immune system’s response to cancer before,” said Lili Yang, lead author of the study and a member of the Eli and Edythe Center for Regenerative Medicine and Stem Cell Research at UCLA. . “What’s especially exciting is that it’s a very well-studied and safe class of drugs, so reusing it for cancer isn’t as difficult as it would be to develop a completely new drug.”

Recent advances in understanding how seeks and destroys naturally , as well as how tumors try to evade this response, have led to new cancer immunotherapies, drugs that increase the activity of the immune system to try to fight cancer.

In an effort to develop new cancer immunotherapies, Yang and colleagues compared from melanoma tumors in mice to immune ones of cancer-free animals. Immune cells that had infiltrated tumors had much higher activity than a gene called monoamine oxidase A or MAOA. The corresponding MAOA protein, called MAO-A, controls serotonin levels and is targeted by MAOI drugs.

“For a long time, people have been theorizing about the cross-talk between the nervous system and the immune system and the similarities between the two,” said Yang, who is also an associate professor of microbiology, immunology and molecular genetics at UCLA. of the UCLA Jonsson Comprehensive Cancer Center. “So it was exciting to find that MAOA was so active in these immune cells that they infiltrated tumors.”

The researchers then studied mice that did not produce MAO-A protein in immune cells. The scientists found that these mice better controlled the growth of melanoma and colon tumors. They also found that normal mice were better able to fight these cancers when treated with MAOIs.

Deepening the effects of MAO-A on the immune system, the researchers found that T cells, the immune cells that target cancer cells to destroy them, produce MAO-A when they recognize the tumors, which decreases their ability to fight cancer.

This finding places MAO-A among a growing list of molecules known as , which are molecules produced as part of a normal immune response to prevent T cells from overreacting or attacking healthy tissues in the body. Cancer is known to exploit the activity of other previously identified immune checkpoints to elude the attack of the immune system.

A la Scientific immunology paper, scientists report that MAOIs help block the function of MAO-A, which helps T cells overcome the immune checkpoint and fight cancer more effectively.

But drugs also play a second role in the immune system, Yang found. Rogue immune cells known as tumor-associated macrophages often help tumors bypass the immune system by preventing antitumor cells, including T cells, from making an effective attack. High levels of these macrophages associated with immunosuppressive tumors of a tumor have been associated with poorer prognoses for people with some types of cancer.

But researchers found that MAOIs block macrophages associated with immunosuppressive tumors, effectively breaking a line of defense that tumors have against the human immune system. This finding is reported in Communications on Nature paper.

“It turns out that MAOIs appear to directly help T cells do their job and prevent tumor-associated macrophages from slowing down T cells,” Yang said.

Combination of MAOIs with existing immunotherapies

Yang said he suspects MAOIs may work well in conjunction with a type of cancer immunotherapy called immune checkpoint blocking therapies, most of which work by targeting immune checkpoint molecules on the surface. of immune cells. This is because MAOIs work on MAO-A proteins, which are found inside cells and function differently from other known molecules at the immune checkpoint.

Studies in mice showed that any of the three existing MAOIs (phenelzine, chlorgillin, or mocolobemide) either by themselves or in combination with a form of immune checkpoint blocking therapy known as PD-1 blockers, could stop or slow the growth of colon cancer and melanoma.

Although they have not tested the drugs in humans, the researchers analyzed clinical data from people with melanoma, colon, lung, cervical and pancreatic cancer; found that people with higher levels of MAOA gene expression in their tumors had, on average, shorter survival times. This suggests that MAOA targeting with MAOIs could help treat a wide range of cancers.

Yang and his collaborators are already planning additional studies to test the effectiveness of MAOIs to increase the response of human immune cells to various cancers.

Yang said MAOIs could potentially act on the brain and immune cells in cancer patients, who are up to four times more likely than the general population to experience depression.

“We suspect that reusing MAOIs for cancer immunotherapy may provide patients with antidepressant and antitumor benefits,” he said.

The combined experimental therapy of the study has been used only in preclinical trials and has not been studied in humans nor has it been approved by the Food and Drug Administration as safe and effective for use in humans. The newly identified therapeutic strategy is covered by a patent application filed by the UCLA Technology Development Group on behalf of the Regents of the University of California, with Yang, Xi Wang and Yu-Chen Wang as co-inventors.

New treatment for late-stage colorectal cancer is effective in preclinical models

More information:
Communications on Nature (2021). DOI: 10.1038 / s41467-021-23164-2

Citation: The drug commonly used as an antidepressant helps fight cancer in mice (2021, June 10) recovered on June 10, 2021 at -antidepressant-cancer-mice.html

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