As men age, their blood cells sometimes lose the very thing that makes them male: the Y chromosome. And that regularly results in aggressive forms of cancer.
In humans, each cell normally has one pair of sex chromosomes. Males have one X and one Y chromosome, while females have two X chromosomes. But sometimes the male Y chromosomes can suddenly disappear from the blood cells. And that has far-reaching consequences a new study On. Because this allows cancer cells to proliferate.
The loss of the Y chromosome
The disappearance of the Y chromosome from blood cells mainly occurs in older men and smokers. “It is the most common human mutation, with 10 percent, 20 percent, and >50 percent of men aged 70, 80, and 90 years, respectively, losing the entire Y chromosome in >10 percent of their blood cells,” said lead researcher Dan Theodorescu. On Scientias.nl. The loss of the Y chromosome was discovered two decades ago and has long been considered insignificant. But recent studies have shown that it may be associated with a shorter lifespan and a higher risk of cancer. “Unfortunately, no one yet knows why the Y chromosome is lost in some people,” says Theodorescu. “There is only some evidence that it may be related to smoking and the genetic background.”
Study
In the new study, researchers took a closer look at the link between the disappearance of the Y chromosome and cancer. Because why are these two apparently inextricably linked? The researchers conducted several in-depth studies, studying cancer cells in animals as well as human tumors. And the team eventually found that the loss of the Y chromosome helps cancer cells evade the body’s immune system.
immune system
This means that when the Y chromosome disappears from blood cells, the body’s ability to fight cancer is hindered. This then regularly results in aggressive bladder cancer. “Our study is the first to link the loss of the Y chromosome to the immune system’s response to cancer,” says Theodorescu. “We found that the loss of the Y chromosome allows bladder cancer cells to evade the immune system and grow very aggressively.”
More about bladder cancer
Bladder cancer is a serious disease in which a malignant tumor grows in the bladder. This condition is almost three times more common in men than in women. The annoying thing is that the disease often only gives symptoms when the tumor has been there for some time. Bladder cancer is the 10th most common cancer. In 2020, some 549,000 cases were reported worldwide, of which 200,000 people died.
The researchers then studied the tumors in more detail. And that has led to further new insights. “We found that the loss of Y chromosome changes T cell function,” explains Theodorescu. “It basically depletes the T cells.”
T cells
It means that T-cells can no longer do their job properly. And that is disastrous. T cells are immune cells that try to get rid of the cancer cells in the body. They recognize the cancer cells with their ‘feeler’, the T-cell receptor. The feeler on the T cell checks if cells look different than normal. If the feeler recognizes a cancer cell, the T cell produces substances to kill the cancer cell. But when T cells are put on hold, they can no longer fight cancer cells either. “And without T cells to fight cancer, the tumor grows aggressively,” says Theodorescu.
Other cancers
All in all, the researchers show how the loss of the Y chromosome can lead to an aggressive form of bladder cancer. The team hypothesizes that the disappearance of the male sex chromosome is an adaptive strategy developed by tumor cells to evade the immune system and survive in multiple organs. And it may not just be about bladder cancer. “Preliminary data show that loss of the Y chromosome can also lead to an aggressive form of prostate cancer,” says Theodorescu.
Achilles heel
Fortunately, these aggressive cancers also have an Achilles’ heel. “They are more sensitive to a treatment called ‘checkpoint inhibitor immunotherapy’ compared to cancers with an intact Y chromosome,” says Theodorescu. “This is one of the most common forms of immunotherapy for cancer in general.” This therapy reverses T-cell exhaustion and activates the immune system. This enables the immune system to fight cancer again.
Tests
The newly gained insights contribute to our basic understanding of the biology of cancer. And so they could have far-reaching implications for the future treatment of this debilitating disease. “From now on we could test for the loss of the Y chromosome,” suggests Theodorescu. “We may then be able to better predict which patients are eligible for treatment with checkpoint inhibitors. This fits the picture of ‘precision medicine’.” Within the healthcare sector, this means that medical treatment is tailored to the individual characteristics of a patient and everyone is served ‘tailor-made’. “This allows us to provide patients with the most effective treatments, while at the same time not treating patients who do not benefit,” says Theodorescu.
Prevent
Further research is needed to better understand the link between the disappearance of the male sex hormone and the depletion of T cells. “If we understand those mechanics, we could even prevent T-cell depletion completely,” says Theodorescu. “Now it can be partially reversed with checkpoint inhibitors, but if we can prevent it in the first place, the prognosis of cancer patients will look much better.”
Women
Although women don’t have a Y chromosome, Theodorescu says the findings from this study may have implications for them as well. The Y chromosome contains a series of related genes on the X chromosome, and these can play a role in both women and men. Additional research is needed to determine what that role might be.
With the study, researchers have confirmed a long-standing suspicion. “We have now shown for the first time that the disappearance of the Y chromosome gives a tumor the ability to evade the immune system,” summarizes Theodorescu. “To our knowledge, this is the first time we have shown a cause-and-effect relationship between loss of the Y chromosome and aggressive cancer growth. Before our study, this was just a possible connection.” According to the researcher, it is very important that we know this now. “The fundamental new knowledge we present here may explain why certain cancers are more severe in men or women and how best to treat them,” argues Theodorescu. “It illustrates that the Y chromosome does more than just determine a person’s biological sex.”
2023-06-30 06:30:44
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