Killer cells improve with age

Photo: d. Annette Liss (right) and Dorina Zuffel (left) from the University of Saarland study how killer cell activity changes as cells age. Until now it was widely assumed that the ability of killer T cells to destroy cancer cells and pathogens would decline with age. However, it turns out that the opposite is true – they become better killers, the older they get.
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Credit: Oliver Dietz

The human immune system is a surprising thing. Until now it was widely assumed that the ability of killer T cells to destroy cancer cells and pathogens would decline with age. However, it turns out that the opposite is true – they become better killers, the older they get. This surprising finding is the result of research conducted by pharmacologist Dr. Annette Liss and molecular biologist Dorina Zuffel at Saarland University. Their work suggests that T cells for older patients could be of particular value in cancer immunotherapy. The results of the study, which help us to better understand how the human immune system progresses, were published in the journal ‘cell aging“.

The older a person is, the more likely they are to develop cancer. According to the German Robert Koch Institute, more than half of the approximately 500,000 people diagnosed with cancer each year are over the age of 60. As the coronavirus pandemic has clearly demonstrated, viral infections tend to be more severe in older patients. This was thought to indicate that the human immune system becomes weaker with age, and thus the same must be true for killer T cells, which play a critical role in fighting pathogens. The job of a T cell is to track down and kill virus-infected or cancerous cells in the body. Until now, the accepted scientific view was that T cells function less effectively with age.

However, researchers at Saarland University have now discovered that T cells turn out to be the ultimate killers as they age. We found the rather surprising finding of CD8’s cytotoxic ability+ T cells to destroy cancer cells do not deteriorate but actually improve with age. When you compare the same number of small and large T cells, the older cells are the better and more effective killers,” said Dr. Annette Lis, a qualified pharmacist who has worked for many years in the group led by Prof. Marcus Hoth at the University Medical Center in Homburg. Dr. Lis was studying How killer cell activity changes with age.

The reason why T cells are such effective killers is largely due to the highly potent weapons they have at their disposal: “The production of perforin and granzyme molecules is enhanced in older T cells. As its name suggests, the perforin molecule perforates target cells resulting in the formation of tiny pores in the cell membrane. Granzyme can then enter cells and initiate apoptosis – a form of programmed cell death. which researches the aging of T cells.

In addition, older experienced T cells have an accurate picture of who they are supposed to target. CD8 cytotoxic+ T cells have a good memory of those who attacked and destroyed in the past. And as part of our adaptive immune system, they live and learn. T cells are able to form memory cells. “If they deal with a pathogen that they are already familiar with, they respond very quickly and very effectively,” Dorina Zuffel said.

For a long time, the oldest memory CD8+ T cells were not thought to be particularly suitable for immunotherapy and therefore found only limited use. In younger cancer patients, these T cells are extracted from the patient’s blood, trained in a petri dish to fight cancer cells and then reintroduced into the patient’s body to fight cancer. The results of the Homburg research group suggest that this type of therapy can also be very useful when treating older cancer patients. “Contrary to expectations, the use of older T cells in adaptive immunotherapy appears to be very promising, especially in treating older patients, and may improve therapeutic efficacy and extend patient life,” said Annette Lees.

But this begs the question of why older adults are not protected from cancer cells and viruses if their T cells are so strong. Like most organs in the body, our immune system is constantly aging, and as it ages, its ability to respond effectively to new pathogens deteriorates. This aging process is referred to in medical research as immunodeficiency and describes the gradual decline in the functioning of our immune cells as we age, “ Lis explained. There has not been enough research done to reveal the exact details of this aging process.

The work of the Homburg research group has now contributed one more piece to the puzzle of understanding these highly complex processes and interactions. On the other hand, we have age-related processes that occur naturally as the cell ages, but we also have to take into account changes in cell function due to the aging of the cell environment. In the case of T cells, the evidence seems to suggest that the cause of the deterioration of the immune response is not to be found in the T cells themselves but in the aging environment. As we age, the number of CD8 . memory goes up+ The T cells that are formed also decline, so that fewer killer cells are available to ward off attack by invading pathogens.

Our results appear to suggest that older, more robust T cells, able to eliminate pathogens or tumor cells more quickly, could compensate for other age-related deficits in elderly patients. So despite the fact that the number of T cells is generally lower in older patients, this smaller army of old, highly potent T cells can still be effective in fighting cancer or viral infections. Dörina Zöphel explained that we are currently carrying out further studies to confirm this hypothesis. The findings by the city of Homburg researchers could provide a basis for new therapeutic procedures in the future.

Study “ faster cytotoxicity with age: increased levels of perforin and granzyme in cytotoxic CD8+ T-cells Promote the Elimination of Cancerous cells” by Dorina Zuffel and Dr. Annette Lees by examining age-related changes in the ability of killer T-cells to destroy cancer cells. Other researchers who contributed to the publication include researchers in biophysics (Prof. Dr. Marcus Huth) and cellular neurophysiology at the Center for Integrative Physiology and Molecular Medicine at Saarland University.Cell Aging, doi:


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