Researchers at Mass General Brigham have uncovered evidence that the thymus, a small immune system organ long thought to lose its importance after childhood, may play a major role in adult health. Two new studies found that adults with healthier thymuses were more likely to live longer and less likely to develop serious diseases. The research also suggests that thymic health may influence how well cancer patients respond to immunotherapy.
The findings were published in two papers in the same issue of Nature and challenge decades of assumptions about the thymus. The results indicate that the organ remains important throughout adulthood and could eventually help guide disease prevention strategies and cancer treatment decisions.
“The thymus has been overlooked for decades and may be a missing piece in explaining why people age differently, and why cancer treatments fail in some patients,” said Hugo Aerts, PhD, corresponding author on the papers and director of the Artificial Intelligence in Medicine (AIM) Program at Mass General Brigham. “Our findings suggest thymic health deserves much more attention and may open new avenues for understanding how to protect the immune system as we age.”
What the Thymus Does
Located in the chest, the thymus helps train T cells, a type of immune cell that helps defend the body against infections and disease. Because the organ gradually shrinks after puberty and produces fewer new T cells over time, many scientists assumed it played only a limited role in adult health.
As a result, the thymus has received relatively little attention in large population studies. Earlier research connected T cell diversity to aging and declining immune function, but those studies were typically small and focused on blood samples.
The new research took a much broader approach. Investigators analyzed data from more than 25,000 adults participating in a national lung cancer screening trial, along with more than 2,500 people enrolled in the Framingham Heart Study, a long-running study that tracks the health of generally healthy adults.
AI Reveals Links to Longevity and Disease Risk
Using artificial intelligence (AI) to evaluate routine CT scans, the researchers measured the size, structure, and composition of the thymus. From those measurements, they created a “thymic health” score.
People with higher thymic health scores experienced significantly better outcomes. Compared with individuals who had poorer thymic health, they had about a 50% lower risk of death from any cause, a 63% lower risk of death from cardiovascular disease, and a 36% lower risk of developing lung cancer. These relationships remained strong even after accounting for age and other health factors.
The researchers believe that declines in thymic health may reduce T cell diversity, making it harder for the immune system to recognize and respond to new threats such as cancer and other diseases.
Their analysis also identified several factors associated with poorer thymic health, including chronic inflammation, smoking, and higher body weight. These findings suggest that lifestyle factors and ongoing inflammation may affect the immune system’s ability to remain resilient over time.
Thymus Health and Cancer Immunotherapy
In a separate study, the team examined CT scans and clinical outcomes from more than 1,200 cancer patients treated with immunotherapy.
The results showed that patients with healthier thymuses tended to respond better to treatment. They faced about a 37% lower risk of cancer progression and a 44% lower risk of death, even after researchers adjusted for differences in patients, tumors, and treatment approaches.
According to the researchers, these findings highlight a potentially important but previously underrecognized role for the thymus in determining how effectively modern cancer immunotherapies work.
More Research Needed
The scientists emphasize that additional studies will be needed to confirm the results. They also note that the imaging technique used to measure thymic health is not yet ready for routine use in clinical practice.
Although lifestyle factors were associated with thymic health, the studies did not investigate whether changing those factors can directly improve thymus function.
The research team is continuing to explore other influences on thymic health. One ongoing study is examining whether unintended radiation exposure to the thymus during lung cancer treatment could affect patient outcomes.
“Improving our understanding and monitoring of thymic health could eventually help physicians better assess disease risk and guide treatment decisions,” said Aerts.
In addition to Aerts, study co-authors of the overall adult health paper include Simon Bernatz, Vasco Prudente, Suraj Pai, Asbjørn Kjær, Yumeng Cao, Jiachen Chen, Asya Lyass, PhD, Borek Foldyna, Leonard Nürnberg, Christopher Abbosh, Charles Swanton, Mariam Jamal-Hanjani, MD, PhD, Michael T. Lu, Joanne M. Murabito, Kathryn L. Lunetta, and Nicolai J Birkbak.
Aerts’ co-authors of the immunotherapy outcomes paper include Simon Bernatz, Vasco Prudente, Suraj Pai, Asbjørn Kjær, Alessandro Di Federico, Andrew Rowan, Selvaraju Veeriah, Lars Dyrskjøt, Leonard Nürnberg, Joao V. Alessi, Patrick A. Ott, Elad Sharon, Allan Hackshaw, Nicholas McGranahan, Christopher Abbosh, Raymond H. Mak, Danielle Bitterman, Mark Awad, Biagio Ricciuti, Charles Swanton, Mariam Jamal-Hanjani, and Nicolai J Birkbak, PhD.
This research received funding support from the National Institutes of Health, European Research Council, Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), Lundbeck Foundation, Novo Nordisk Foundation, and Savvaerksejer Jeppe Juhl og Hustru Ovita Juhl Research Stipend.