Ageing is a natural process, and so is the loss of the Y chromosome. Recently, Cedars-Sinai Cancer Center, Los Angeles made a groundbreaking discovery. They found that the loss of the Y Chromosome in a male’s cells – a common aspect of the ageing process – allows cancer cells to evade detection by the body’s immune system.
In a study published in Nature, Cedars-Sinai detailed their findings. The theory was tested on individuals where it was found that the loss of the Y chromosome resulted in aggressive bladder cancer. However, the researchers also found that this loss also made the disease more responsive to a standard cancer treatment called immune checkpoint inhibitors.
“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,” Dan Theodorescu, MD, PhD, a corresponding author of the study and the person who initiated the research, said in a statement.
In men, some cells lose the Y chromosome as they age. This happens in about 10 per cent to 40 per cent of bladder cancers. The Y chromosome contains important genes, and its loss affects how cancer cells grow.
Slowing bladder cancer growth
In studying individuals with bladder cancer, the researchers found that those with Y chromosome loss had a tough time fighting the cancer without immune checkpoint inhibitors. But when they received this treatment, their chance at survival improved considerably.
In the lab, they tested the cancer cells in mice and saw that the ones without the Y chromosome grew faster when the mice had a working immune system. This suggested that Y chromosome loss weakens the immune system’s ability to fight cancer.
The exciting part is that immune checkpoint inhibitors helped slow down the cancer’s growth despite it being aggressive. These inhibitors give the immune system a boost, making it better at attacking cancer.
“Our investigators postulate that loss of the Y chromosome is an adaptive strategy that tumour cells have developed to evade the immune system and survive in multiple organs,” explains Shlomo Melmed, MB, ChB, executive vice president of Academic Affairs and dean of the Medical Faculty at Cedars-Sinai.
Chromosomes and cancer
This discovery is a big step in understanding how the Y chromosome affects cancer and how it can be addressed better. The researchers will now study the genetic link between Y chromosome loss and the immune system’s weakness. They hope they will find ways to prevent this problem and improve cancer treatment.
Although this study was done only with men, the findings might be relevant for women too. The Y chromosome has related genes on the X chromosome, which could play a role in cancer growth for both genders.
