Forgotten organ found to be key to longer life and chance of successful cancer treatment

By using artificial intelligence (AI) to analyse routine CT scans, the researchers discovered previously unknown links between the health of the thymus in adults and factors such as lifespan and ageing, and the risk of cardiovascular disease and cancer. The scientists also found that the thymus may influence the response to immunotherapy - a cancer treatment that depends on the strengths of a patient’s immune system. The findings suggest that the thymus plays a far more important role in adult health than previously assumed. The results could open up new possibilities for personalising disease prevention and cancer treatment.

‘The thymus has been overlooked for decades and may be a missing piece of the puzzle in understanding why people age differently and why some cancer treatments work better than others,’ says Professor Hugo Aerts of Maastricht University and Harvard University, senior author of both studies. ‘Our findings suggest that the health of the thymus deserves much more attention and could open up new possibilities for understanding how we can better protect the immune system as people grow older.’
 

Training immune cells

The thymus is a small organ in the chest that ‘trains’ so-called T cells, preparing the immune system to protect the body against infections and disease. For decades, it was assumed that the organ becomes largely inactive after puberty, as it shrinks with age and produces less diverse T cells. As a result, the role of the thymus in adult health has rarely been studied on a large scale.

Previous research had linked T-cell diversity to ageing and the decline of the immune system, but most studies were based on relatively small analyses of blood samples. In contrast, for their research, the scientists in Maastricht and the United States analysed data from more than 25,000 adults in a lung cancer screening study and from more than 2,500 participants in the so-called Framingham Heart Study, a large, long-running population study of predominantly healthy adults in the United States.

‘Instead of only looking at immune cells in the blood, we wondered whether it might be better to study the organ that produces and “trains” these cells, and to examine how healthy the thymus appears on a radiological scan,’ says Aerts. ‘In other words, we assessed the source rather than just the output.’
 

Health of the thymus

The research team analysed the size, shape, and composition of the thymus and developed a so-called ‘thymus health score’. People with a high health score were about 50% less likely to die, 63% less likely to die from cardiovascular disease and 36% less likely to develop lung cancer compared with people with a low score. These associations remained significant even after adjusting for age, sex and other health factors.

According to the researchers, when thymus health and T-cell diversity decline, the immune system may be less able to respond to new threats such as cancer or other diseases. Chronic inflammation, smoking, and higher body weight were found to be associated with poorer thymus health. This suggests that lifestyle and systemic inflammation may influence the resilience of the immune system throughout life.
 

Cancer treatment

In a second study, the researchers analysed CT scans and treatment outcomes in cancer patients receiving immunotherapy. Patients with better thymus health had about 37% lower risk of disease progression and 44% lower risk of death, even after adjusting for other patient, tumour, and treatment factors. This suggests that the thymus may play a previously unrecognized role in how well patients respond to modern cancer immunotherapy, a treatment whose success depends in part on activating specific T cells in the patient.

‘The thymus has long been underestimated,’ says Professor Lizza Hendriks of Maastricht University, a pulmonologist specialising in lung cancer at Maastricht University Medical Center+, who was not involved in the study. ‘These results suggest that the thymus plays a much more important role than was thought, and that a better understanding of this organ could potentially benefit patients.’

The researchers stress that the results still need to be confirmed in future studies and that the imaging method is not yet ready for routine clinical use. Although lifestyle factors were associated with thymus health, the study didn’t show whether lifestyle changes can actually improve thymus function.

‘If the thymus isn’t functioning properly, the immune system may be less well prepared to fight off new threats such as cancer,’ says Aerts. ‘A better understanding and monitoring of thymus health could, in the future, help doctors assess disease risks more accurately, and support them in making treatment decisions.’