Researchers have found that the loss of Y chromosomes as men age hampers the body’s ability to fight bladder cancer.
The study, published in the scientific journal Nature, found that loss of the Y chromosome helps bladder cancer cells evade the body’s immune system, said the researchers from Cedars-Sinai Medical Center.
“This study for the first time makes a connection that has never been made before between loss of the Y chromosome and the immune system’s response to cancer,” said Dan Theodorescu, director of Cedars-Sinai Cancer, who initiated the research.
“We discovered that loss of the Y chromosome allows bladder cancer cells to elude the immune system and grow very aggressively.”
In humans, each cell normally has one pair of sex chromosomes; men have one X and one Y chromosome, while women have two X chromosomes. In men, loss of the Y chromosome has been observed in several cancer types, including 10 per cent – 40 per cent of bladder cancers. Loss of the Y chromosome also has been associated with heart disease and Alzheimer’s disease.
The Y chromosome contains the blueprints for certain genes. Based on the way these genes are expressed in normal cells in the bladder lining, investigators developed a scoring system to measure loss of the Y chromosome in cancers.
The team reviewed data on two groups of men. One group had muscle invasive bladder cancer and had their bladders removed, but were not treated with an immune checkpoint inhibitor — a standard bladder cancer treatment.
The other group participated in a clinical trial and were treated with an immune checkpoint inhibitor. The results showed that patients with loss of the Y chromosome had poorer prognosis in the first group but much better overall survival rates in the latter.
To determine why this happens, the investigators grew cancer cells in a dish where the cells were not exposed to immune cells. The researchers also grew the diseased cells in mice that were missing a type of immune cell called T-cells. In both cases, tumours with and without the Y chromosome grew at the same rate.
In mice with intact immune systems, tumours lacking the Y chromosome grew at a much faster rate than did tumours with the intact Y chromosome.
“The fact that we only see a difference in growth rate when the immune system is in play is the key to the ‘loss-of-Y’ effect in bladder cancer,” Theodorescu said. “These results imply that when cells lose the Y chromosome, they exhaust T-cells. And without T-cells to fight the cancer, the tumour grows aggressively.”
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