TCD scientists discover how ‘natural killer’ cells target cancer

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.

 

UL Study Finds Irish Mothers Struggle To Recognise Overweight Or Obesity In Their Children

A University of Limerick study has found that mothers of overweight and obese children struggle to recognize their child as overweight or obese.

The study reported on 7,655 mothers and their nine year old children using data from the national longitudinal study of children, Growing Up in Ireland. Study co-author, Professor Ailish Hannigan, highlighted that “while three quarters of overweight mothers and 60% of obese mothers in the study recognised themselves as overweight or obese, mothers of overweight or obese children were much less likely to recognise this in their child.” Just 1 in 6 mothers of obese children classified their child as moderately or very overweight.

“Interestingly, overweight or obese mothers with accurate perceptions of their own weight were more likely to correctly classify their overweight or obese child”, said study co-author, Dr. Helen Purtill. The public health significance of the study was highlighted by Dr. Kieran Dowd, Centre for Physical Activity and Health Research, University of Limerick “If mothers, who are the primary caregivers in the majority of Irish homes, are unable to identify their child as overweight or obese, it is unlikely that they will react or intervene to change this. This may result in continued weight gain throughout the remainder of childhood and adolescence into adulthood”.

“Open and honest discussions between health professionals and parents about the child’s weight status should be encouraged”, said study co-author Professor Clodagh O’Gorman, “together with practical strategies for helping the family maintain a healthy weight. Importantly, weight control measures aimed at children should be family-based and include all family members.”

The research, which was published in the international journal Archives of Disease in Childhood was conducted by a multidisciplinary research team at the University of Limerick composed of Dr Kieran Dowd (Department of Physical Education and Sport Sciences), Mr Robert Kirwan (Graduate Entry Medical School), Professor Ailish Hannigan (Graduate Entry Medical School), Dr. Helen Purtill (Department of Mathematics and Statistics), and Professor Clodagh O’Gorman (Graduate Entry Medical School).