When most of us think of the organs that are vital to our health, some that easily come to mind are the heart, lungs, liver, or brain.
But according to several recent studies led by Mass General Brigham researchers, there’s another often‑overlooked organ that sits just above the heart, quietly working behind the scenes to help our immune system, having previously unknown impacts on our health.
If you guessed the thymus, you are correct (or you read the headline of this blog post first—either way, congratulations!).
What is the Thymus?
The thymus is an organ of the immune system that plays a key role in childhood and early development, where it facilitates the maturation of T cells, an important part of the body’s defense against germs and other foreign invaders.
After puberty, the thymus begins to shrink and is gradually replaced by fatty tissue, a process known as thymic involution. This age‑related transformation makes the adult thymus appear inactive or largely absent, which has led to a misunderstanding of its ongoing function and physiological relevance in human health.
Now, two teams of researchers at Mass General Brigham (MGB) are redefining the importance of the thymus in adult human health—and forming a new scientific partnership in the process.
Is the Thmyus Relevent for Overall Adult Health?
During the early months of the COVID-19 pandemic, hematology/oncology researchers David Scadden, MD, PhD, and colleagues Karin Gustafsson, PhD, and Kameron Kooshesh, MD, were unable to go into their wet lab at Massachusetts General Hospital due to stay-at-home restrictions.
The group was used to fast‑paced, hands‑on experiments, and needed a project that could keep their momentum going, but also one that could be done remotely.
Kooshesh began digging into MGB’s clinical databases, and together with the team, focused in on a question: Is the thymus relevant for overall health in adults?
At the beginning, no one thought it would lead to a major finding.
“I didn’t have high expectations for this project,” Scadden recalls. “But we figured, you know, let’s see what happens,”
Their investigation turned out to be more interesting than anticipated, however.
After the team reviewed thousands of patient records, they found that adults who had their thymus surgically removed had poorer survival outcomes and a higher chance of developing cancer.
What started as a temporary project soon developed into a focused scientific effort that led to a New England Journal of Medicine publication —the first formal evidence that the adult thymus has a major impact on cancer outcomes and overall health — and has continued through additional peer‑reviewed studies led by Gustafsson.
“This was very far from what the lab normally does,” says Gustafasson, “It's been an interesting but quite rewarding journey.”
The discovery led the lab to a simple and well‑validated blood test to measure thymus activity in adults.
The test detects tiny leftover pieces of DNA that appear only in newly formed T cells.
These DNA “tags” do not get copied when T cells divide, so they provide a precise marker of how many fresh T cells the thymus is producing, and provide a window into the strength of a patient's immune system.
Artificial Intelligence Amplifies the Importance of the Thymus
Three years ago, Hugo Aerts, PhD, director of the Artificial Intelligence in Medicine (AIM) Program at Mass General Brigham, also set his lab’s sights on the thymus.
Hugo Aerts, PhD
The AIM program harnesses artificial intelligence (AI) to develop new algorithms that analyze routinely captured medical information, such as imaging scans, and identify new ways to identify disease risk.
His lab has recently uncovered that AI can detect markers of heart attack risk from routine CT scans, and that even a simple selfie could be used to determine a person’s biological age and predict survival outcomes in patients treated for cancer.
Aerts and team first turned their attention to the thymus was during a brainstorming session on finding ways to measure T cells with AI to predict how a person with cancer might respond to treatment.
T cells could not be seen on CT scans, so the research team started pondering other avenues that might serve as proxy targets. The discussion soon turned to the thymus, which could be visualized easily on CT.
“The thymus had been assumed to be irrelevant in adulthood, but [this assumption] was because there was no way to see a direct link between it and disease,” explains Aerts. “With AI, we could look at large cohorts and detect these subtle signals.”
The researchers developed a new algorithm focused on the size and shape of the thymus, generating a “thymic health” score.
They used the score to analyze chest CT scans from more than 25,000 adults in a national lung screening trial and over 2,500 participants in the Framingham Heart Study.
These studies track patients for many years, ensuring a rich source of data on their overall health.
Aerts and team found that people with higher thymic health scores had a 50% lower risk of death, 63% lower risk of cardiovascular death, and 36% lower risk of developing lung cancer, compared to those with low thymic health. Their findings were recently published in Nature (and highlighted in the video below).
“The most important thing about this paper is that it informs the scientific community that this organ could be much more important than we previously thought,” says Aerts. “We hope that this will lead to much more research into the health of the thymus is its importance for longevity.”
Aerts, a member of the Department of Radiation Oncology at Mass General Brigham, then employed the algorithm people on people who received cancer treatment, hypothesizing, like the Scadden lab, that the immune function of a healthy thymus may impact treatment outcomes.
In a second paper published in the same Nature issue, the team compared CT scans and outcomes in more than 1,200 immunotherapy-treated patients, finding those with strong thymic health had a 35% lower risk of cancer progression and 44% lower risk of death.
Their findings suggest that having a healthy thymus may contribute to a person responding better to immunotherapy.
Since learning about their shared research efforts, the Aerts and Scadden labs have formed a collaboration to advance their findings, with a shared focus on identifying ways to improve thymus health.
It's a scientific partnership that spans two different departments within Mass General Brigham, blending the latest in information technology with traditional bench science. "It's a match made in heaven," says Aerts.
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