09 February 2018

The ageing immune system may play a far bigger role in the development of cancer than previously thought, according to a research project linking Scottish and French researchers.

Researchers from the University of Dundee, Heriot Watt University, the University of Edinburgh, in Scotland, and the Institut Curie in France, believe if their findings are proven to be correct – and immune system changes are a more important indicator than gene mutations – it could change the way that cancer is treated and viewed.

The researchers examined data on two million cases of cancer affecting people in the 18-70 age range. They developed a mathematical model for the expected increase in cancer incidence in relation to the age-related decline of the immune system, comparing it to the age profiles for 100 different cancers.

Writing in the latest edition of the Proceedings of the National Academy of Sciences, they found their model fitted the data better than the multiple mutation hypothesis.

As the immune system generally declines more slowly in women than men, this could also account for the gender difference in cancer incidence, they report.

Senior author Dr Thea Newman, formerly vice principal of research and professor of biophysics and systems biology at Dundee, said: “This is still very early days but if we are proven right then you could be talking about a whole new way to treat and prevent cancer.

“Nearly all of the mainstream research into cancer is based on how we can understand genetic mutations, target them and thereby cure the disease. We're not debating the fact that mutations cause cancer, but are asking whether mutations alone can account for the rapid rise in cancer incidence with age when ageing causes other profound changes in the body.”

The team tested their model on data from the US-based National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) programme.

The results showed that many cancers appear to be very strongly linked to the decline of the immune system, while others are more likely linked to a combination of immune system decline and multiple mutations.

One of the main causes of the ageing immune system ageing is the shrinking of the thymus gland, which is where T cells are produced.

This process begins from about the age of one year and it halves in size every 16 years, resulting in a corresponding reduction in the production of T cells.

The researchers found a very strong correlation between the chances of certain cancers increasing and the new T cell populations falling.

Dr Sam Palmer, formerly of the University of Dundee and now Heriot Watt University, said: “The immunosurveillance hypothesis is that cancer cells are continually arising in the body but that normally the immune system kills them before a new tumour is able to establish itself.

“The T cells are constantly scanning for cancer cells, looking to destroy them. If they can't find them soon enough or the immune system is weak then the cancer population has the chance to grow. The chances of this happening will increase with age as the thymus is shrinking all the time.

“For our model, we imagined a war between T cells and cancer cells, which the cancer cells win if they grow beyond a certain threshold. We then set this threshold to be declining with age, proportional to T cell production. This simple hypothesis turns out to be able to explain much of the cancer incidence data.”

Professor Clare Blackburn of the University of Edinburgh, added: “We believe that our findings are extremely relevant and show the need to take the immune system even more seriously in cancer research.”

Source: Thymic involution and rising disease incidence with age. PNAS 5 February 2018

Link: http://www.pnas.org/cgi/doi/10.1073/pnas.1714478115


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