Scientists hope this research may one day be used to help reinvigorate the body’s defences by redirecting the immune response back to tumours.
New cancer research led by scientists at Trinity College Dublin has uncovered a mechanism related to certain kinds of carcinomas that is causing cancer-killing natural killer (NK) cells to be redirected away from their target tumours.
Published in the Journal of Immunology, the study found that the most obese cancer patients had the lowest number of NK cells in their tumours. NK cells can directly kill tumour cells and so represent an area of interest in developing future therapeutic approaches.
The Trinity team worked with participants from the gastric centre in St James’s Hospital and examined tissue samples from the blood, fat and tumours of those with oesophagogastric adenocarcinoma (OAC).
It was with this cohort that the research showed an inverse correlation between visceral obesity and NK cells in tumours. The research suggested that these cells are instead migrating towards visceral fat tissue, such as the fat around the stomach.
OACs are a group of obesity-associated and inflammation-driven cancers. The survival rates are often very low, researchers said, with the five-year survival rates for oesophageal adenocarcinoma and gastric adenocarcinoma at 20pc and 32pc, respectively.
Their research identified a biological pathway that could potentially be targeted by drugs to stop this unhelpful movement of NK cells and instead direct them towards tumours to help the body deal with the cancer.
Lead researchers Dr Melissa Conroy and Dr Joanne Lysaght from Trinity’s School of Medicine hope that their work could result in new therapies for aiding in the body’s own anti-cancer immune response.
“For the first time our team has shown that the most viscerally obese oesophageal and gastric cancer patients have the lowest number of crucial cancer-killing natural killer cells in their tumours, and our work has confirmed that visceral obesity in these patients has devastating consequences for the anti-cancer immune response,” said Conroy.
“The natural killer cells are pulled into the visceral fat of these patients by a protein called fractalkine where they are altered and even depleted. Consequently, the cancer-killing immune cells cannot reach and fight the tumour in sufficient numbers. Importantly, we have shown that the movement of natural killer cells to the visceral fat of such cancer patients can be significantly reduced by a drug targeting fractalkine.”
Conroy emphasised that while there is still a long process to go from a discovery like this to therapeutic results, it was nonetheless an exciting and promising finding that could one day mean providing a treatment option for people who have this cancer prognosis.