The thymus, a butterfly-shaped organ that sits between our collarbones, has never seemed like a particularly useful appendage—at least in adults. During early childhood, it provides a place for T cells (the T stands for thymus) to mature into immune cells that attack invaders. But during adolescence the organ begins to shrink and mostly stops producing these cells. By adulthood, it’s assumed to be so useless that cardiac surgeons will occasionally remove it just to get easier access to the heart.
But researchers have recently started to question that assumption, and a study published today in The New England Journal of Medicine, refutes it outright: The thymus may in fact be crucial for adults, and removing it could prove fatal.
The new work is very welcome, says Marcel van den Brink, an immunologist at Memorial Sloan Kettering Cancer Center who wasn’t involved in the study. Very little research on adult thymus function exists, he notes. “[The new study] basically confirms something many people have thought, but we never had good evidence for it.”
To gauge the importance of the thymus in adults, Harvard University hematologist David Scadden and his colleagues analyzed medical records from nearly 2300 people who had undergone chest surgeries at Massachusetts General Hospital. Half had had thymectomies, usually performed to treat thymus cancer or certain autoimmune conditions such as myasthenia gravis, in which T cells attack the body and cause muscle weakness.
Compared with the other chest surgery patients, those who underwent a thymectomy were almost three times more likely to die from a variety of causes, from infectious disease to cancer, during the next 5 years, the team found. They also had twice the risk of cancer, which tended to be more aggressive than cancers that developed in people who retained their thymuses. The trend persisted even when the researchers looked only at people who had no history of cancer or myasthenia gravis, suggesting the thymectomy itself led to increased death rates.
Next, the scientists looked at how thymus removal affected the immune system. Much like antibodies, each T cell attacks only one type of molecule such as a protein on the surface of a virus or bacterium. When the researchers compared blood plasma from 22 people whose thymuses had been removed with plasma from 19 control patients, they found the thymectomy patients had fewer biological markers that indicated the body was producing new, different types of T cells. That suggests that even adult thymuses can still produce new kinds of mature T cells. The thymectomy patients’ plasma also contained more molecules that trigger inflammation, suggesting the patients could be developing autoimmune disorders.
A lack of T cell diversity likely makes people more susceptible to infectious disease, Scadden says, particularly to pathogens such as SARS-CoV-2 that they never encountered as children when their thymuses were most active. Without a thymus, the immune system would have a harder time developing T cells to target the new threat. He suspects that vaccines may also be less effective in these individuals because they can’t raise an effective immune response, although this has never been studied directly.
“This experiment is elegant,” says Dong-Ming Su, an immunologist at the University of North Texas Health Science Center at Fort Worth who was not involved with the work. The finding, he says, provides strong evidence that the thymus is still functional in adults. Su suspects that a thymectomy may shorten people’s life spans overall, although the current study did not follow its subjects long enough to find out.
The increased cancer rates in patients with thymus removal also suggest T cells from the thymus play an important role in responding to and preventing cancer, van den Brink adds. And the procedure may be more harmful in adults, he says, because children’s thymuses seem to regenerate themselves.
Other research has recently shown that tonsil removal, which is also common in children, may harm the immune system long term and lead to increased risks of infectious diseases, allergies, and respiratory diseases. But although both organs may have been underappreciated, Scadden says the tonsils and thymus are very different: Immune cells elsewhere in the body could at least partially compensate for the loss of tonsils in the respiratory tract. But only the thymus can produce new types of mature T cells.
Future research could determine whether gene or cell therapies could restore thymus function in people who have it removed, Su says.
Scadden says the next step is to determine whether people who have a better functioning thymus remain healthier as they age—no one has studied the degree to which thymus function differs among adults. He is also looking into the implications of thymectomy for people receiving stem cell transplants, in which the immune cell–producing bone marrow is removed and the immune system has to re-create itself from scratch.
Scadden hopes the findings will lead to a reassessment of clinical guidelines around thymus removal, especially when it isn’t strictly necessary. “I think it should raise a level of concern for the downsides of thymectomy, which hadn’t been front and center.”
