Researchers in Oxford have uncovered new insights into why the most aggressive oesophageal cancers are so difficult to treat and how the body’s own defence systems are helping them to thrive.
The study, led by Professor Eileen Parkes in the University of Oxford’s Department of Oncology, analysed patient-donated tumour samples and found that the most dangerous types of oesophageal cancers share a key feature: high chromosomal instability. This means the cancer cells constantly make mistakes as they grow and divide, making them more aggressive, harder to treat and allowing them to adapt more easily.
The research, which was supported by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC), was published in Science Advances.
The research team discovered that this chromosomal instability does not just make the cancer grow faster; it also changes how the tumour interacts with the body’s own defence systems.
Using newly developed laboratory models of oesophageal cancer, the researchers found that cancers with unstable chromosomes ‘switch on’ certain genes. These genes were shown to send out chemical signals that attracted inflammatory immune cells into the tumour, bolstering its defence.
“We’ve known for some time that chromosomal instability makes cancer more aggressive, but what we’ve discovered is that it also fuels inflammation in oesophageal cancer in a way that actually helps the tumour,” said Dr Bruno Beernaert, postdoctoral researcher in Professor Parkes’s lab.
“Instead of triggering an effective immune attack against itself, the cancer appears to hijack the body’s own defence systems, the immune response, to help it to survive treatment and spread.”
The findings may help to explain why some of the most aggressive types of oesophageal cancers are particularly resistant to existing therapies and point to new potential treatment strategies.
Professor Parkes added: “By uncovering how chromosomal instability reshapes the tumour’s immune environment, we’ve identified a potential vulnerability. If we can disrupt this inflammation pathway, we may be able to suggest new treatment options which improve outcomes for patients.”
As well as the Oxford BRC, this research was supported by Cancer Research UK and the Wellcome Trust.