Findings may explain why people with obesity have impaired capacity to fight disease
Kevin O’Sullivan
Scientists at Trinity College, Dublin have worked out how a biological engine that powers cancer-killing cells functions.
Crucially, their research highlights how that engine is fuelled and confirms the presence of cholesterol-like molecules act as a “cut-off” switch, making it hard for our “natural killer” (NK) cells in the body to act against cancer. This is particularly so with patients that have cancer and are obese.
The scientists, led by Dr David Finlay, assistant professor in immunometabolism at TCD, have published their findings in the journal Nature Immunology. They outline a previously unknown metabolic switch, which is essential for initiating the anti-tumour actions of NK cells. These are immune cells that play an important role in defences against cancer, as they can directly kill tumour cells.
Once activated – eg by proteins known as cytokines which occur with inflammation – NK cells increase uptake of cellular fuel, which is then converted into energy which powers the all-important tumour-killing machinery.
The research shows activated NK cells use a very different engine configuration to that observed in other immune cells, and that the key factor that switches NK cells to this engine configuration is a protein called an SREBP.
Similar to cholesterol
When the scientists used oxysterols, which are very similar to cholesterol, to prevent this switch from activating, NK cells failed to kill tumour cells.
Dr Finlay said: “The function of SREBP – the key factor that controls the energy production in natural killer cells and thus fuels their activity – is known to be blocked by cholesterol and cholesterol-like molecules called oxysterols. Therefore, our findings reveal a previously-unknown way by which the cancer-killing functions of natural killer cells can be disrupted.”
As tumour cells can produce oxysterols and cholesterol, and levels tend to be higher in people with obesity, the scientists believe they may now have part of the explanation for why NK cells typically perform poorly in patients living with cancer and obesity.
“The next step is to investigate whether the functions of NK cells are indeed impaired in individuals with high cholesterol level, and whether cholesterol-lowering interventions can restore NK cell function in these individuals,” Dr Finlay added.
