Tumours that house an abnormal number of DNA bundles could impact how well immunotherapies perform. 

The discovery was made through a study carried out by Harvard Medical School researchers which investigated 5,000 tumour samples from 12 different types of cancer from the Cancer Genome Atlas – a massive US tumour sample database.

The team found that those tumours with aneuploidy, i.e. an abnormal number of chromosomes, housed a higher number of active genes that encourage growth and multiplication.

In addition, aneuploid samples exhibited fewer immune cells, suggesting immune cells were struggling to detect the cancerous cells.

“These findings strongly suggest that aneuploidy helps tumours evade detection by the immune system,” said Professor Charles Swanton, from the Francis Crick Institute in London. “[They] might lead to ways of targeting this feature of human cancers which leads to such poor survival in patients.”

In order to confirm their findings, the team then looked at data from two trials investigating the use of anti–CTLA-4 immunotherapy in melanoma patients.

The team found that those melanoma samples with a higher level of aneuploidy correlated with a poorer treatment response.

Immunotherapies are generating plenty of excitement in the cancer field due to their mechanism and effectiveness. Unlike traditional treatments, immunotherapies harness the patient’s own immune system to make them detect cancer cells in the body. The idea is to create a lasting immune response similar to that seen in the body when it encounters the same foreign body twice.

Although the technology is promising, not every patient will respond as well as others.

These new findings suggest that an aneuploidy screening test could help establish those who will respond better to immunotherapies than others, better informing doctor treatment decisions and opening a new area for researchers to investigate.

“This work suggests that we need to continue exploring how aneuploidy comes about and how it is maintained,” added Swanton. “If we can do that, then it might lead to ways of targeting this feature of human cancers which leads to such poor survival in patients.”

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