Cancer-killing cells are diverted into fat and away from tumours in obese cancer patients

Posted on: 09 August 2021

The most obese cancer patients have the lowest number of cancer-killing Natural Killer (NK) cells in their tumours. That is according to new research, which also identifies a biological pathway that can be targeted with drugs to mitigate the unhelpful migration of NK cells away from the tumours where they can fight the cancer.

In combination, the findings, which have just been published in the Journal of Immunology, offer significant hope that a new therapeutic approach may one day make a difference by redirecting and reinvigorating the anti-cancer immune response.

Oesophagogastric adenocarcinoma (OAC)

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

OACs are a group of obesity-associated and inflammation-driven cancers. Sadly, survival rates are very low: five-year survival rates for oesophageal adenocarcinoma and gastric adenocarcinoma are 20 and 32% respectively and this is largely due to poor treatment response rates of <30%, highlighting the need for new and additional treatment options.

Fractalkine – a possible target

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.

Crucially, the scientists identified that a protein called Fractalkine plays a key role in both pulling the NK cells into the visceral fat and altering their activity. They showed experimentally that this pathway can be targeted with drugs to reduce the extent to which the NK cells are erroneously diverted from the tumours.

Dr Melissa 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.”

This research was supported by funding from Breakthrough Cancer Research and the Irish Research Council.

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