Doctrine refuted: The thymus gland located behind the breastbone was previously considered largely superfluous in adults. But now a study reveals that if this immune organ is removed, for example during heart surgery, this has significant health effects: those affected are more likely to develop cancer and their risk of premature death is 2.9 times higher. In addition, an intact thymus gland also seems to reduce the risk of autoimmune diseases, as researchers report in the “New England Journal of Medicine”.
The thymus, also known as the thymus gland, sits behind our breastbone and plays an important role in our adaptive immune system, especially in childhood. It is in this gland that the immature T cell precursors produced in the bone marrow are prepared for their future tasks: they mature and differentiate into the various types of T defense cells. During this imprinting phase, the immune cells learn, among other things, to distinguish the body’s own cell characteristics from foreign ones.
More fat than function?
But according to conventional wisdom, this task of the thymus gland ends with puberty: the organ gradually loses its immune function and turns into fatty tissue over the course of life. “In adults, the thymus is therefore usually considered non-functional and is sometimes removed during cardiac surgery to gain better access to the heart and large blood vessels,” explain Kameron Kooshesh of Massachusetts General Hospital in Boston and his colleagues.
In order to find out whether the thymus in adults is really superfluous and can be removed without consequences, Kooshesh and his team investigated this in a long-term study. To do this, they measured the risk of cancer, an autoimmune disease, and death over several years in 1,146 patients who had had their thymus gland removed for heart surgery and in 1,146 controls who had similar characteristics, diseases and surgeries, but theirs thymus retained.
Increased risk of cancer, autoimmune diseases and death
The result: Contrary to what was thought, the removal of the thymus gland does have an impact on health – even in adults. “We discovered that the thymus is absolutely necessary for health,” reports senior author David Scadden of Massachusetts General Hospital. “If it is missing, people have at least twice the risk of dying or developing cancer.” According to the study data, the risk of developing an autoimmune disease is 1.5 times higher.
Specifically, after five years of the study, 8.1 percent of the test subjects without a thymus gland had died, compared to only 2.8 percent of the control group with a thymus gland, which was comparable in terms of age, state of health and surgery. That equates to a 2.9-fold increased risk of death, the team reports. During the same time, 7.4 percent of patients without a thymus developed cancer, compared to 3.7 percent in the control group – only about half as many.
Similarly significant differences were found in an additional comparative analysis with the mortality and cancer rates of the general US population: Again, the risk for test subjects without a thymus gland was almost twice as high as for people with this organ.
Fewer T helper cells and T killer cells
According to the physicians, these results confirm that the thymus gland is by no means without function in adults either – and continues to play an important role in the immune system. An indication of this was also provided by a supplementary analysis in which the researchers examined the T-cell production and immune functions in 22 patients without a thymus and 19 comparison persons with the gland in more detail.
It turned out that the immune system produced almost three times less new CD4 in test persons without a thymus gland+– and CD8+-Lymphocytes. These are two important subtypes of T cells: The CD8+-T cells are the “killer cells” that destroy infected or degenerated cells and thus fight infections or tumors directly. The CD4+– or T-helper cells activate the T-killer cells and at the same time give the B-cells the necessary information so that they can produce suitable antibodies.
The role of residual thymic activity should be further explored
Kooshesh and his team therefore advocate examining the role of the thymus in the immune system and health of adults more closely than has been the case up to now. They suspect that even after large parts of the organ have been converted into adipose tissue, there is still residual activity that is important for long-term health. “Therefore, it should be considered very carefully before having surgery to remove the thymus gland,” says Scadden.
The research team now wants to next investigate whether and how the activity of the thymus differs in adults and how this affects health. “We can test the relative fitness of the thymus and determine whether its level of activity is associated with better health,” explains Kooshesh. (New England Journal of Medicine, 2023; doi: 10.1056/NEJMoa2302892)
Source: Massachusetts General Hospital