At a glance
Imaging studies of more than 27,000 adults link a healthier thymus on CT scans with a longer life and lower risks of cardiovascular disease and lung cancer.
Across 3,400 cancer patients, thymic health strongly predicted immunotherapy response and survival, beyond standard tumor biomarkers.
Smoking, obesity, metabolic syndrome, and chronic inflammation were tied to poorer thymic health, pointing to potentially modifiable drivers of immune aging.
Two new studies challenge a decades-old assumption that the thymus, an organ best known for its role in establishing immune function in childhood, becomes irrelevant in adulthood.
Using artificial intelligence to analyze thousands of routine CT scans, a team led by Harvard Medical School researchers uncovered that adults with a healthy-appearing thymus lived longer and had lower rates of cardiovascular disease and cancer than those with an unhealthy thymus. In a separate study of patients with cancer, the researchers found that thymic health may influence response to immunotherapy — a treatment that depends on the strength of a patient’s immune system.
These findings, published March 18 in the same issue of Nature, suggest the thymus plays a far more consequential role in adult health than previously understood and might provide a new target for personalizing disease prevention and cancer treatments.
“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, corresponding author on both papers, HMS professor of radiation oncology at Dana-Farber Cancer Institute, and director of the Artificial Intelligence in Medicine 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,” he said.
Thymic health and risk of age-related disease
The thymus is a small organ in the chest that helps train T cells, priming the immune system to protect the body from infections and disease. For decades, doctors believed the organ was mostly inactive after puberty because it shrinks with age and produces fewer new T cells. As a result, its role in adult health has rarely been examined in large populations.
Previous research has linked T-cell diversity to aging and immune decline, but most of those studies relied on small, blood-based analyses. In contrast, the new studies examined more than 25,000 adults in a national lung cancer screening trial and more than 2,500 participants in the Framingham Heart Study — a large, long-running population cohort of generally healthy adults.
The team used a deep-learning model to analyze the size, shape, and composition of the thymus in participants’ CT scans and generate a “thymic health” score. People with high thymic health scores had about a 50 percent lower risk of premature death, 63 percent lower risk of cardiovascular death, and 36 percent lower risk of developing lung cancer compared to those with low thymic health. These associations remained significant after adjusting for age and other health factors. The team saw similar patterns across many other causes of death, suggesting that thymic health may reflect overall immune resilience.
The researchers theorize that when thymic health and T-cell diversity decline, the immune system becomes less able to respond to new threats, like cancer or other diseases.
Their analysis found that chronic inflammation, smoking, and high body weight were associated with poorer thymic health, suggesting that lifestyle and systemic inflammation may influence immune resilience across the lifespan. In the Framingham cohort, lower thymic health was also linked to features of metabolic syndrome (including higher blood pressure, blood sugar, and triglycerides), higher levels of inflammatory proteins in the blood, and greater frailty and disability risk.
Predicting cancer immunotherapy response
In the second study, the researchers analyzed CT scans and outcomes from more than 1,200 immunotherapy-treated patients. Patients with stronger thymic health according to the AI score had about a 37 percent lower risk of cancer progression and a 44 percent lower risk of death than those with lower thymic health scores, even after accounting for other patient, tumor, and treatment factors.
These findings point to a previously underappreciated role the thymus may play in shaping how well patients respond to modern cancer immunotherapies.
The team also validated the imaging measure in an independent clinical trial cohort. This showed that higher thymic health scores were associated with laboratory markers of continued T-cell production, greater T-cell diversity in blood and tumors, and stronger activity of immune pathways, supporting thymic health as a proxy for immune competence.
Next steps for thymus-focused care
The researchers caution that their findings will need to be confirmed in future studies and that the imaging method is not yet ready for routine clinical use. While lifestyle factors were linked to thymic health, the studies did not test whether modifying those factors can directly improve thymic function.
The team is currently leading additional research to investigate whether other care-associated factors, such as unintended radiation exposure to the thymus, may impact thymic health and treatment outcomes.
“Improving our understanding and monitoring of thymic health could eventually help physicians better assess disease risk and guide treatment decisions,” said Aerts.
Authorship, funding, disclosures
Study co-authors of the overall adult health paper include Simon Bernatz, Vasco Prudente, Suraj Pai, Asbjørn Kjær, Yumeng Cao, Jiachen Chen, Asya Lyass, Borek Foldyna, Leonard Nürnberg, Christopher Abbosh, Charles Swanton, Mariam Jamal-Hanjani, Michael T. Lu, Joanne M. Murabito, Kathryn L. Lunetta, and Nicolai J. Birkbak.
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.
These studies were supported by the National Institutes of Health (grants U24CA194354, U01CA190234, U01CA209414, R35CA22052, K08DE030216-01, R01AG067457, 75N92019D0031), the European Research Council, the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), the Lundbeck Foundation, the Novo Nordisk Foundation, and the Savvaerksejer Jeppe Juhl og Hustru Ovita Juhl Research Stipend.
A full list of disclosures can be found in the papers.
