Antidepressants may help the immune system fight cancer

Antidepressants are commonly associated with improving mood and mental health. But recent research suggests they may also have an unexpected effect: helping the immune system fight cancer.

Scientists from the University of California, Los Angeles (UCLA) found that a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) significantly boost the cancer-fighting abilities of T cells.

In both mouse and human tumor models, SSRIs were shown to suppress tumor growth across multiple types of cancer.

Serotonin’s cancer-fighting role

“It turns out SSRIs don’t just make our brains happier; they also make our T cells happier – even while they’re fighting tumors,” said Dr. Lili Yang, UCLA professor of Microbiology, Immunology & Molecular Genetics.

“These drugs have been widely and safely used to treat depression for decades, so repurposing them for cancer would be a lot easier than developing an entirely new therapy.”

SSRIs, which include well-known medications like Prozac and Celexa, work by blocking a protein called serotonin transporter (SERT). This action increases levels of serotonin, often called the “happiness hormone,” in the brain. However, serotonin also plays a vital role in other bodily functions, including digestion, metabolism, and immune responses.

The team began exploring serotonin’s connection to cancer after noticing that immune cells from tumors had more serotonin-regulating molecules than expected. Their attention turned to an enzyme called MAO-A, which breaks down serotonin and other neurotransmitters.

Depression drugs to tumor fighters

Back in 2021, the team discovered that when T cells detect tumors, they produce MAO-A, which limits their effectiveness.

In mouse models with melanoma and colon cancer, treating with MAO inhibitors (MAOIs) – another class of antidepressants – improved the T cells’ cancer-fighting abilities.

But MAOIs come with risks. They can cause severe side effects and interact dangerously with certain foods and medications. That concern led the team to explore SERT, a molecule with a simpler role – transporting serotonin.

“Unlike MAO-A, which breaks down multiple neurotransmitters, SERT has one job – to transport serotonin,” explained Dr. Bo Li, assistant researcher at UCLA. “SERT made for an especially attractive target because the drugs that act on it – SSRIs – are widely used with minimal side effects.”

Antidepressants tested on cancer

To test the theory, the researchers used SSRIs in models of melanoma, breast, prostate, colon, and bladder cancer.

The results were promising. Tumors shrank by more than 50% on average. At the same time, T cells became more efficient at killing cancer cells.

“SSRIs made the killer T cells happier in the otherwise oppressive tumor environment by increasing their access to serotonin signals, reinvigorating them to fight and kill cancer cells,” Yang said.

Mood drugs aid immunotherapy

The study didn’t stop there. The researchers also wanted to see if SSRIs could improve the effects of existing cancer treatments.

The experts combined an SSRI with an immune checkpoint blockade (ICB) therapy -specifically, an anti-PD-1 antibody. ICB therapies remove the brakes from immune cells, helping them target tumors more aggressively.

The combination had dramatic results. Tumor size was significantly reduced in all test cases, and some mice went into complete remission.

“Immune checkpoint blockades are effective in fewer than 25% of patients,” said James Elsten-Brown, a researcher and PhD student at UCLA. “If a safe, widely available drug like an SSRI could make these therapies more effective, it would be hugely impactful.”

Rethinking antidepressant side benefit

The researchers now plan to study cancer patients who are already taking SSRIs, especially those undergoing ICB therapy. The goal is to determine whether these patients show improved outcomes.

“Since around 20% of cancer patients take antidepressants – most commonly SSRIs – we see a unique opportunity to explore how these drugs might improve cancer outcomes,” Yang said. “Our goal is to design a clinical trial to compare treatment outcomes between cancer patients who take these medications and those who do not.”

This approach could also lower the cost and speed up the development of cancer treatments. Because SSRIs are already FDA-approved, they don’t need the same rigorous testing as new drugs.

“Studies estimate the bench-to-bedside pipeline for new cancer therapies costs an average of $1.5 billion,” Yang added. “When you compare this to the estimated $300 million cost to repurpose FDA-approved drugs, it’s clear why this approach has so much potential.”

The full study was published in the journal Cell.

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