High cholesterol could aid cancer spread
Cholesterol is found in every cell of the body and has important natural functions when it comes to digesting foods, producing hormones, and generating vitamin D.
Scientists at Trinity College Dublin have discovered the engine that powers cancer-killing cells and that it can be switched off by cholesterol-like molecules. Natural killer cells are immune cells that play a major role in the body’s defence against cancer, as they can directly kill tumour cells.
The scientists believe they may now have part of the explanation of why natural killer cells usually perform poorly in patients with obesity and those living with cancer.
The scientists, led by Ussher assistant professor in immunometabolism at TCD, David Finlay, have just published their findings in the leading journal .
“The next step is to investigate whether the functions of natural killer cells are indeed impaired in individuals with high cholesterol levels and whether cholesterol-lowering interventions can restore natural killer cell function in these individuals,” said Dr Finlay.
The scientists have found a previously unknown metabolic switch, which is essential for initiating the anti- tumour action of natural killer cells.
Once activated, natural killer cells increase their uptake of cellular fuel, which is converted into energy by a biochemical engine that powers an all-important tumour-killing machinery of the natural killer cells.
The research shows that activated natural killer cells use a very different engine configuration to that seen in other immune cells.
A key factor that switches natural killer cells to the engine configuration is a protein called srebp. When scientists used oxysterols to block the switch, the natural killer cells failed to kill tumour cells.
“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,” said Dr Finlay.
“Therefore, our findings reveal a previously unknown way by which the cancer-killing functions of natural killer cells can be disrupted.”
Dr Finlay said the study had taken around three years, and the next step would be to test whether people with high cholesterol had a poor killer cell response. The experiments have been primarily conducted on mice but a number used natural killer cells taken from healthy people.
The scientists want to continue their research with additional funding. They want to “ramp up” their study of human cells of both healthy people and people with high cholesterol.
Dr Finlay said certain types of cancer would be treated with antibodies that recognise the disease but they rely on cells, like natural killers cells coming along, identifying the antibody and then killing the cells.
“Natural killer cells are really important for some of these new immuno-therapies,” he said. “But nobody ever considers what the cholesterol levels are in those patients.”
It could be the therapies are not working very well for patients with high cholesterol and one way to address that would be to consider their cholesterol levels first and change their diet.
