2023-06-22 14:10:05
As they age, some cells in the body in men lose the Y chromosome (the element that makes them biologically male), and that loss allows cancer cells to evade the body’s immune system and grow easily.
This is the main conclusion of an investigation by the Cedars-Sinai Cancer Center (Los Angeles, California) published this Wednesday in Nature.
The study has found that this common effect of aging in men results in aggressive bladder cancerbut it also makes the disease more responsive to an immunotherapy treatment called ‘immune checkpoint inhibitors’.
A connection between the loss of the Y chromosome and the immune system’s response to cancer is established for the first time
Researchers are already developing a test to detect loss of the Y chromosome in tumors to help doctors adapt treatment with inhibitors of immune checkpoints for male patients with bladder cancer.
“This study establishes for the first time a never-before-established connection between Y-chromosome loss and the immune system’s response to cancer.” Dan Theodorescudirector of Cedars-Sinai Cancer Center and lead author of the study.
Dan Theodorescu, director of the Cedars-Sinai Cancer Center and lead author of the research. / Cedars-Sinai Medical Center
“We discovered that the loss of the Y chromosome allows bladder cancer cells bypass the immune system and grow very aggressively,” says the researcher.
Men and women, different chromosomes
In humans, each cell has a pair of sex chromosomes: males have one X and one Y chromosome, and females have two X chromosomes.
Loss of the Y chromosome allows bladder cancer cells to evade the immune system
Dan Theodorescu, main author
In males, loss of the Y chromosome has been linked to various types of cancerespecially that of the bladder, but this loss is also associated with heart disease and Alzheimer’s disease.
The Y chromosome contains blueprints of certain genes. Based on the way these genes are expressed in normal cells lining the bladder, the researchers developed a scoring system to measure Y chromosome loss in cancers.
They then reviewed data from two groups of men, one with bladder cancer who had his bladder removed and was not treated with immune checkpoint inhibitors, and another who participated in a clinical trial and received treatment with this immunotherapy treatment.
They found that patients with Y chromosome loss had a worse prognosis in the first group and much better overall survival rates in the second.
To find out why this was happening, they compared the growth rates of bladder cancer cells with cells from laboratory mice.
Patients treated with immunotherapy had a better prognosis than those who had their bladder removed
The team cultivated tumor cells that were not exposed to immune cells and also grew diseased cells in mice lacking immune cells called T cells. In both cases, tumors with and without the Y chromosome they grew at the same rate.
However, in mice with intact immune systems, tumors lacking the Y chromosome grew at a much faster pace than tumors with an intact Y chromosome.
“These results imply that when cells lose the Y chromosome, deplete T cells. And without T cells to fight the cancer, the tumor grows aggressively,” concludes Theodorescu.
When cells lose the Y chromosome, they deplete the T cells, and without them the tumor grows aggressively.
Dan Theodorescu
The team also concluded that tumors lacking the Y chromosome, while more aggressive, they were also more vulnerable and responded better to immune checkpoint inhibitors.
This therapy, one of the two main treatments available for bladder cancer, reverses T cell depletion and enables the body’s immune system to fight cancer.
Researchers believe that loss of the Y chromosome is an adaptive strategy of tumor cells to evade the immune system and survive in multiple organs, although they acknowledge that further work is needed to understand the genetic connection between Y chromosome loss and T cell depletion.
Reference:
Theodorescu, D. “Y chromosome loss in cancer drives growth by evasion of adaptive immunity” Nature (2023)
Fuente: EFE
Rights: Creative Commons.
#Loss #chromosome #age #men #promotes #cancer #growth