A commonly used class of antidepressants could enhance the immune system’s ability to combat cancer, according to new research from UCLA published in *Cell*. The study found that selective serotonin reuptake inhibitors (SSRIs) significantly improved T cells’ ability to fight tumors and reduced tumor growth across multiple cancer types in both mouse and human models.
“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, senior author and a member of UCLA’s Broad Center of Regenerative Medicine and Stem Cell Research. “These drugs have been widely and safely used to treat depression for decades, so repurposing them for cancer would be far easier than developing new therapies.”
SSRIs, sold under brands like Prozac and Celexa, are the most prescribed antidepressants in the U.S., with one in eight adults taking such medications, per the CDC. They work by blocking the serotonin transporter (SERT), a protein that regulates levels of serotonin — the “happiness hormone” — thereby increasing serotonin availability in the brain.
Beyond its role in mood, serotonin influences bodily processes including digestion, metabolism, and immune function. Yang’s team turned to SERT after earlier research on another serotonin-regulating molecule, MAO-A, which breaks down neurotransmitters but is linked to safety concerns. Unlike MAO-A, SERT specifically transports serotonin, making it a safer target.
Tests of SSRIs on models of melanoma, breast, prostate, colon, and bladder cancer showed the drugs reduced average tumor size by over 50% and enhanced the effectiveness of killer T cells — the immune system’s cancer-fighting cells. “SSRIs made killer T cells happier in the oppressive tumor environment by increasing their access to serotonin, reinvigorating them to fight,” explained Yang, a professor at UCLA’s Jonsson Comprehensive Cancer Center.
Combining SSRIs with existing therapies showed even greater promise. In mouse models of melanoma and colon cancer, pairing an SSRI with anti-PD-1 antibody — a common immune checkpoint blockade (ICB) therapy — significantly reduced tumors and achieved complete remission in some cases. “ICBs work in fewer than 25% of patients,” noted co-author James Elsten-Brown. “A safe, widely available drug like an SSRI could make these therapies far more impactful.”
The team plans to investigate real-world outcomes in cancer patients taking SSRIs, particularly those on ICB therapies, and aims to launch a clinical trial comparing outcomes between users and non-users of the drugs. Repurposing FDA-approved drugs could accelerate progress: Yang noted new cancer therapies cost an average $1.5 billion to develop, versus an estimated $300 million to repurpose existing drugs.
A patent application for the therapeutic strategy has been filed by UCLA, with Yang and first author Dr. Bo Li as co-inventors. The research was funded by organizations including the National Institutes of Health and the California Institute for Regenerative Medicine.
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