Obese patients have lowest number of cancer-killing cells, new Trinity research finds

Eilish O'Regan

Patients who are most obese have the lowest number of cancer-killing cells in their tumours, new research from Trinity College revealed today.

They do not have enough of what are known as National Killer (NK) cells. NK cells are specialised while blood cells which scientists say act as the immune system's assassins.

A team of scientists led by Dr Melissa Conroy and Dr Joanne Lysaght from Trinity College Dublin’s School of Medicine, worked with blood, fat, and tumour tissue samples collected from oesophagogastric adenocarcinoma (OAC) patients.

They were being treated at the National Oesophageal and Gastric Centre at St James’s Hospital.

However, their research also identified a biological pathway that can be targeted with drugs to reduce the unhelpful migration of NK cells away from the tumours where they can fight the cancer .

The findings in the Journal of Immunology, provide hope that a new therapeutic approach may one day make a difference by redirecting and reinvigorating the anti-cancer immune response.

OACs are a group of obesity-associated and inflammation-driven cancers with very low survival rates.

The five-year survival rates for oesophageal adenocarcinoma and gastric adenocarcinoma are 20 and 32pc respectively and this is largely due to poor treatment response rates of less than 30pc.

The team of scientists discovered an inverse correlation between visceral obesity and NK cells in tumours, such that the most obese patients have the lowest number of NK cells in their tumours.

They found a protein called Fractalkine plays a key role in both pulling the NK cells into the visceral fat and altering their activity. In experiments they showed this pathway can be targeted with drugs to reduce the extent to which the NK cells are erroneously diverted from the tumours.

Dr Conroy said: “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.

“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.

“Although it takes considerable time to go from a discovery like this to bringing a new drug to patients, it is nonetheless very exciting that our work strongly suggests a therapeutic approach targeting the fractalkine pathway would have significant utility in redirecting and reinvigorating the anti-cancer immune response in these poor prognosis cancers.”