For decades, the thymus (a small immune organ located behind the breastbone) was thought to become largely irrelevant after childhood. But two recent Nature studies from investigators at Mass General Brigham have challenged that long-held assumption, demonstrating that thymic health is strongly associated with longevity, cardiovascular disease, cancer risk, and response to cancer immunotherapy.
Now, in a new study published in Annals of Oncology , the same research team reports that unintended radiation exposure to the thymus during treatment for lung cancer is associated with worse clinical outcomes, suggesting that protecting the thymus may become an important consideration during radiation treatment.
"Our recent studies showed that the adult thymus is far more important than medicine has appreciated," said co-senior author Hugo Aerts, PhD, director of the Artificial Intelligence in Medicine (AIM) Program at Mass General Brigham. "This naturally led to the next question: If the thymus plays such an important role in immune health, should we also be protecting it during cancer treatment?"
The thymus is responsible for producing and educating T cells, the immune cells that recognize infections and cancer. Although the organ gradually shrinks with age, the team's recent Nature studies showed that many adults retain measurable thymic function throughout life , and that healthier thymuses are associated with lower mortality, lower risk of cardiovascular disease and cancer, and improved responses to modern immunotherapies.
Although the thymus is not intentionally targeted during radiation therapy, it often lies close to tumors in the chest and therefore receives substantial incidental radiation exposure. Whether this unintended radiation affects the immune system or influences patient outcomes has remained largely unknown. To investigate this question, the researchers analyzed CT scans and clinical outcomes from more than a thousand patients with locally advanced non-small cell lung cancer. Using artificial intelligence to analyze routine CT scans, they quantified each patient's thymic health before treatment and measured the amount of radiation delivered to the thymus.
The researchers found that patients whose thymic health was unimpaired before they received radiotherapy had the most favorable outcomes overall. But within this group, those who received higher radiation doses to the thymus had significantly worse overall survival and a greater risk of developing distant metastatic disease. Follow-up imaging showed declines in thymic health among patients who received higher thymic radiation doses.
The findings also supported the team's recent research on immunotherapy. In a previous study, they found that patients with healthier thymuses experienced substantially greater benefit from immune checkpoint inhibitors. In the current study, among patients who received the immunotherapy drug durvalumab, those with preserved thymic health appeared to be particularly affected by radiation delivered to the thymus.
The researchers emphasize that the study is observational and that prospective clinical studies will be needed before thymus-sparing approaches become part of routine clinical practice. However, the findings provide the first large-scale clinical evidence that preserving thymic health during radiation therapy may improve outcomes for patients with lung cancer.
"Together, these studies suggest that the patients who benefit most from immunotherapy may also be the ones who benefit most from protecting the thymus during radiation treatment," said co-senior author Raymond H. Mak, MD, a radiation oncologist with the Mass General Brigham Cancer Institute. "They reinforce the broader concept that successful cancer treatment is not only about eliminating the tumor, but also about preserving the patient's immune system."
Authorship: In addition to Aerts and Mak, study co-authors include Vasco Prudente, Simon Bernatz, Suraj Pai, Katelyn Atkins, Federica Pecci, Edoardo Garbo, Keno Bressem, Christian Guthier, Andrew Warrington, Marion Tonneau, Cosmin Ciausu, Suhong Yu, Leah Thompson, Edward Mannarino, Asbjorn Attermann, Leonard Nuernberg, Christopher Kehayias, Christopher Abbosh, Charles Swanton, Mariam Jamal-Hanjani, Biaggio Ricciuti, and Nicolai J Birkbak.
Funding: This research received funding support from the National Institutes of Health National Cancer Institute (U24CA194354, U01CA190234, U01CA209414, R35CA22052); the European Research Council (866504); Deutsche Forschungsgemeinschaft (DFG, German Research Foundation; 502050303); the Lundbeck Foundation (R272-2017-4040); the Novo Nordisk Foundation (NNF21OC0071483, NNF23OC0085954); and the Savvaerksejer Jeppe Juhl og Hustru Ovita Juhl Research Stipend.
Disclosures: Aerts reports consulting fees and/or stock ownership in Onc.AI, Love Health, Sphera, Health-AI, Ambient, and AstraZeneca. Mak reports consulting for AstraZeneca and research funding from AstraZeneca, among other organizations. AstraZeneca manufactures durvalumab, an immunotherapy drug evaluated in one of the study cohorts. Additional author disclosures can be found in the paper.
Papers cited: Prudente, V et al. "Thymic Radiation is Associated with Worse Outcomes in Patients with NSCLC" Annals of Oncology DOI: 10.1016/j.annonc.2026.07.001
