As they get older, some cells of the organism in men lose the chromosome Y (the element that makes them biologically male), and that loss allows cancer cells to can avoid the immune system of organism and grow easily.
This is the main conclusion of an investigation from the Cedars-Sinai Cancer Center (Los Angeles, California) published this Wednesday in Nature.
The study found that this common effect of aging in men leads to aggressive bladder cancerbut it also makes the disease more responsive to an immunotherapy treatment called ‘immunological checkpoint inhibitors’.
Researchers are already developing a test to detect the loss of the Y chromosome in tumors to help clinicians tailor checkpoint inhibitor treatment immune to male patients with bladder cancer.
«This study establishes for the first time a never-before-established connection between loss of the Y chromosome and the immune system’s response to cancer,» says Dan Theodorescu, director of Cedars-Sinai Cancer Center.
«We found that the loss of the Y chromosome allows bladder cancer cells to evade the immune system and grow very aggressively,» says Dan Theodorescu, who led the research.
Men and women have different chromosomes
In humans, each cell has one pair of sex chromosomes: Males have one X and one Y chromosome, and females have two X chromosomes.
In males, the loss of the Y chromosome It has been linked to several types of cancer.especially that of the bladder, but this loss is also associated with heart disease and Alzheimer’s disease.
Y chromosome contains blueprints for certain genes. Based on the way these genes are expressed in normal cells of the bladder lining, the researchers developed a scoring system to measure the loss of the Y chromosome in cancers.
Next, they reviewed data from two groups of men, one with bladder cancer who had his bladder removed and was not tested with immune checkpoint inhibitors, and another who participated in a clinical trial and received treatment with This immunotherapy treatment.
They observed that patients with loss of the Y chromosome had a worse prognosis in the first group and overall survival rates much better in the second.
To find out why this was happening, compared growth rates of bladder cancer cells with cells of laboratory mice.
The team cultivated tumor cells that were not exposed to immune cells and he also grew diseased cells in mice that lacked immune cells called T cells. In both cases, the tumors with and without the Y chromosome grew at the same rate.
However, it is mice with intact immune systemstumors lacking the Y chromosome grew at a much faster rate than tumors with the intact Y chromosome.
«These results imply that when cells lose the Y chromosome, deplete the cells T. And without T cells to fight the cancer, the tumor grows aggressively”, concludes Theodorescu.
The team also concluded that the tumors that were missing the chromosome And, although more aggressive, they were also more vulnerable and more responsive to inhibitors of immune checkpoints.
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.
The researchers believe that chromosome loss and is an adaptive strategy of tumor cells to evade the immune system and survive in multiple organs, though acknowledging that more work is needed to understand the genetic connection between Y chromosome loss and T cell depletion.