Widely used antidepressants could help the immune system fight cancer
A type of drug already taken by more than 8 million people in the UK could help the immune system fight cancer and shrink tumours, a study finds.
The widely used class of antidepressant – selective serotonin reuptake inhibitors, or SSRIs- is used to increase the availability of serotonin in the brain, a neurotransmitter that plays a role in mood, emotion and sleep.
But scientists have also discovered the drug can enhance the ability of T cells, a type of white blood cell, to fight cancer and suppress tumour growth across a range of cancer types.
The study published in the journal Cell by researchers at UCLA in California, looked at both mouse and human tumour models responsible for melanoma, breast, prostate, colon and bladder cancer.
“It turns out SSRIs don’t just make our brains happier; they also make our T cells happier – even while they’re fighting tumours,” said Dr Lili Yang, senior author of the new study and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.
“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.”
While serotonin is best known for the role it plays in the brain, it also plays a role in digestion, metabolism and immune activity.
Dr Yang and her team first began investigating serotonin’s role in fighting cancer after noticing that immune cells isolated from tumours had higher levels of serotonin-regulating molecules.
At first, they focused on MAO-A, an enzyme that breaks down serotonin and other neurotransmitters, including norepinephrine and dopamine.
In 2021, they reported that T cells produce MAO-A when they recognise tumours, which makes it harder for them to fight cancer.
They found that treating mice with melanoma and colon cancer using MAO inhibitors, also called MAOIs – the first class of antidepressant drugs to be invented – helped T cells attack tumours more effectively.
But because MAOIs can cause side-effects and interactions with certain foods, they decided to try a different serotonin-regulating molecule: SERT.
“Unlike MAO-A, which breaks down multiple neurotransmitters, SERT has one job – to transport serotonin,” explained Dr Bo Li, first author of the study and a senior research scientist in the Yang lab.
“SERT made for an especially attractive target because the drugs that act on it – SSRIs – are widely used with minimal side effects,” Dr Li said.
The researchers tested SSRIs in mouse and human tumour models representing melanoma, breast, prostate, colon and bladder cancer and found they reduced tumour size by more than half.
The antidepressants also made cancer-fighting T cells, known as killer T cells, more efficient.
The team also tested the antidepressants alongside existing cancer therapies which work by suppressing immune cell activity to allow T cells to attack T cells more effectively. The combination reduced tumour size in all the treated mice.
However, to confirm these findings the team will need to investigate whether real-world cancer patients taking SSRIs have better outcomes.
