The thymus was long thought to become useless after childhood. But researchers using artificial intelligence (AI) and tens of thousands of computed tomography (CT) scans have found that adults with healthier thymuses appear to be less likely to develop cancer, heart disease and other illnesses linked to ageing.
There is an organ just behind your breastbone you have probably never heard of. Researchers now suspect that this long-neglected organ may help shape how we age – and how well some cancer treatments work.
The thymus acts as a finishing school for immune cells early in life and was long thought to fade into fat during adolescence. In open-heart surgery, it is often scooped out and thrown away. But for some people, the thymus appears to remain active well into adulthood – and even into old age. These people also seem less likely to develop several diseases linked to ageing.
Researchers used AI to assess thymus health in tens of thousands of CT scans. People with healthier thymuses were more likely to survive – and less likely to develop cancer and heart disease – over the following decade.
Their results, published in Nature, suggest that the thymus may play a greater role in age-related illness than scientists previously realised, says co-author Hugo Aerts, Director of the Artificial Intelligence in Medicine (AIM) Program of Harvard University, Cambridge, MA, USA.
“It makes you wonder what else we may have underestimated.”
Finishing school and lifelong learners
Medicine has a long history of underestimating organs beyond the vital five, the researchers agree. “If you take the heart out, you know, you die immediately,” Aerts says, so doctors quickly learned to “leave that in.” The spleen, tonsils and appendix were all once dismissed as vestigial before scientists recognised their roles in immune function.
Scientists only learnt in the 1960s that the thymus is vital in developing a functional immune response during early life. It is where T cells – the frontline defenders of the immune system – mature and learn to distinguish invading pathogens from healthy host cells.
“The thymus is almost the size of the lungs in newborns,” says Nicolai Juul Birk, a professor at the University of Copenhagen who researches cancer immunology.
After peaking around age 12 or 14 years, the thymus undergoes a process called involution – it is invaded by fat cells and gradually becomes difficult to distinguish from surrounding adipose tissue. “Everybody thought that it finished its work in childhood,” Juul says.
The thymus – or what some surgeons regarded as little more than a glob of fat – has often been removed during open-heart surgery simply because it is in the way. But researchers now suspect that removing the thymus could have “very negative consequences 10 or 20 years down the road,” Aerts says.
Then came a provocative possibility. In the early 2010s, Charles Swanton, a professor of oncology at University College London, United Kingdom, suggested that some people might still have an active thymus well into late middle age.
“He proposed that this may help to explain a lot of later-onset disease – age-associated disease and cancer,” Juul says.
27,000 CT scans reveal the thymus in shades of grey
To learn how many adults still have a recognisable thymus, the researchers turned to large banks of chest CT scans collected through long-term studies: the United States’ National Lung Screening Trial and the Framingham Heart Study.
Simon Bernatz, an MD-PhD candidate and radiology resident at Harvard Medical School, painstakingly scored 1,600 CT scans to train AI to distinguish thymuses in various stages of involution from adipose tissue.
They then turned the AI loose on more than 27,000 CT scans from these long-term studies.
“We cannot ask a radiologist to grade 30,000 scans,” Aerts says. “That would be years and years of work.”
The AI performed admirably – “actually better than the human alone,” Aerts says. “A human can say ‘okay, this thymus looks very healthy, or it is completely gone.’ An AI algorithm is much better at saying, ‘this is a 6 out of 10 or a 7 out of 10.’ It can make a much more fine-grained assessment.”
Previous studies had suggested that the thymus is largely gone in adulthood. But the deep learning model instead found evidence of “favourable” thymic health among 75% of participants.
More than a biomarker
The long-term health data from the heart and lung studies means that “we could also show that thymic health was associated with outcomes,” Aerts says.
Even after correcting for age, sex and other factors, people with healthier thymuses had a 50% lower risk of death, a 63% lower risk of cardiovascular death and a 36% lower risk of developing lung cancer over the subsequent 12 years of follow-up.
A companion study, published in the same issue of Nature, offered another clue. People with lung cancer with more robust-looking thymuses had greater T-cell diversity and more T cells that were “recent graduates” from the thymus circulating in their blood.
What the researchers saw on the scans “matches really well to the real-world output of the thymus. It is not just a fancy AI-based biomarker. It actually measures how functional an organ is,” Juul says.
This revelation could also help explain why cancer immunotherapy works better for some people than others. These drugs train the immune system to identify and attack cancer cells. The team then looked at more than 1,200 people receiving immunotherapy for lung cancer. Those with healthier thymuses had a 37% lower risk of cancer progression and a 44% lower risk of death. “It makes a lot of sense,” Juul says. “Immunotherapy is boosting the immune system. If there is not much left to boost, it may not work as well.”
Can you get your thymus checked? And can you help it?
Unfortunately, the researchers say, it is still too early for people to rush off asking for thymus scans – clinicians would not yet know how to interpret the results. “We are working on moving these tools into the clinic,” Aerts says, “first through tie-ins with existing CT programmes like lung cancer screenings in the United States.”
There are no hard and fast rules for the pace of thymic degradation, Aerts explains. “Women have on average a healthier thymus than men of the same age,” and young people generally have stronger thymuses than older people, he says. “But there is still huge variation – a lot of older men still have functioning thymuses, whereas some young women do not.”
They identified a handful of lifestyle factors that appear to affect thymic health, including smoking and body mass index. “Our working hypothesis is that chronic inflammation may drive the process,” Juul says, and everyday habits may either fuel or suppress that inflammation.
“We still need to demonstrate real causality,” Aerts says. “If we improve lifestyle, do we see thymic health improve?”
Since the article was published in March, researchers across disciplines have contacted the team with ideas about how the thymus might influence cancer, metabolic disease and longevity.
“It opens up new possibilities for drug development,” Aerts says.
