Each human cell has two chromosomes, which provide your body with instructions on how to grow and develop from a single cell inside the uterus.
But according to a recent study from the Cedars-Sinai cancer center, chromosomes may be crucial in the fight against disease and serve as the foundation for human life.
On June 21, a group of eminent scientists from across the nation, led by Dan Theodorescu, director of Cedars-Sinai Cancer and the study’s corresponding author, published their findings in Nature.
According to the researchers, male cells have an X and a Y chromosome pair that together form a pair and provide instructions for which genes should be expressed in the body.
Theodorescu stated in a release on June 21 that the study “makes a connection that has never been made before between loss of the Y chromosome and the immune system’s response to cancer.” “We found that loss of the Y chromosome enables bladder cancer cells to escape the immune system and grow extremely aggressively.”
According to the number of Y chromosomes each male possessed, the researchers divided the males into two groups.
Each of the 300 men in the groups had muscle-invasive bladder cancer that was locally advanced, and their ages ranged from 34 to 90.
The release states that the Y chromosome “contains the blueprints for some genes.” Researchers created a scoring system to gauge Y chromosome loss in cancers based on how these genes are expressed in healthy cells of the bladder lining.
The “Y chromosome signature” of the study participants was rated as high or low, and their advancement was monitored over time.
“Patients with (a) low Y chromosome gene expression score had significantly worse overall survival compared with those with higher expression,” the study concluded.
The test revealed that the Y chromosome was involved, but the researchers were unsure of the mechanism. So they ran an additional test on mice.
In mice with healthy immune systems, the researchers cultivated bladder cancer cells. Both mice with complete Y chromosomes and mice lacking Y chromosomes developed tumors.
According to the press release, the researchers discovered that the bladder cancer cells expanded “much faster” in mice with fewer Y chromosomes than those with more.
The ‘loss-of-Y’ effect in bladder cancer can be explained by the fact that we only observe a difference in growth rate when the immune system is active, according to Theodorescu in the press release. These findings suggest that cells exhaust their T-cell supply when they lose the Y chromosome. Additionally, the tumor snowballs in the absence of T cells to fight the disease.
Studies have demonstrated that Y chromosome loss occurs in between 10 and 40 percent of bladder cancers in males, among other cancer types.
Additionally connected to heart disease and Alzheimer’s, two diseases that are more common in older people, is the loss of Y chromosomes.
Hany Abdel-Hafiz stated in the press release, “Fortunately, this aggressive cancer has an Achilles’ heel, in that it is more sensitive to immune checkpoint inhibitors than cancers with an intact Y chromosome.”
Immune checkpoint inhibitors function by stopping T-cell exhaustion brought on by your body’s defenses against cancer cells. According to cancer.net, your body only produces a certain number of T-cells, and if there is too much cancer to fight, the T-cells can’t keep up. T-cells attack cancer cells and cause them to become inflamed and die.
Immune checkpoint inhibitors are one of the most popular bladder cancer treatments because they keep your body’s T-cell count from dropping too low.
Theodorescu stated in the release that although checkpoint inhibitors can partially reverse T-cell exhaustion, preventing it from occurring in the first place would have a significant positive impact on patient outcomes.
Theodorescu claimed that despite the study’s focus on the male-specific Y chromosomes, which can undergo chromosomal changes as well, the results can be applied to all sexes.
“The fundamental new information we present here may explain why and how to treat certain cancers that are more severe in either men or women. It also shows that the Y chromosome is involved in more than just determining human biologic sex, according to Theodorescu.
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