Researchers from the Londsdale Health Institute at Maynooth University, have found that glucagon-like peptide (GLP-1) analogues, can actually restore anticancer immune cells, ‘Natural Killer (NK)’, function in the body including its ability to kill cancerous cells. The research, ‘Glucagon-like peptide-1 therapy in people with obesity restores natural killer cell metabolism and effector function’, published in Obesity, also shows that the restored cancer-killing effect of NK cells is independent of the GLP-1's main weight loss function so it appears the treatment is directly kick-starting the NK cells' engine.
"My team and I are very excited by these new findings in relation to the effects of the GLP-1 treatment on people with obesity and it appears to result in real tangible benefits for those currently on the drug,” explained Dr Andrew E. Hogan, Associate Professor & Principal Investigator, Lonsdale Human Health Institute in Maynooth University. "While these findings will understandably be welcomed by those living with obesity and looking for safe and effective treatments, given the recent spike in popularity related to the benefits of the GLP-1 treatment with global and high-profile celebrities commenting on its success, global demand has increased and resulted in a worldwide shortage of the drug. I hope this is something that is brought under control to ensure as many people as possible living with obesity can start their own treatment of this beneficial drug."
People with obesity (PWO) have functionally defective NK cells, with a decreased capacity to produce cytokines and kill target cells, underpinned by defective cellular metabolism. The researchers hypothesised that the changes in peripheral NK cell activity are contributing to the multimorbidity in PWO, which includes an increased risk of cancer. Therefore, they investigated whether therapy with long-acting GLP-1 analogues, which are an effective treatment for obesity, could restore NK cell functionality in PWO.
In a cohort of 20 PWO, this study investigated whether six months of once weekly GLP-1 therapy (semaglutide) could restore human NK cell function and metabolism using multicolour flow cytometry, enzyme-linked immunosorbent assays, and cytotoxicity assays.
They reported that PWO who received GLP-1 therapy have improved NK cell function, as measured by cytotoxicity and interferon-γ/granzyme B production. The study also demonstrates increases in a CD98-mTOR-glycolysis metabolic axis, which is critical for NK cell cytokine production, and the reported improvements in NK cell function appear to be independent of weight loss.
“Collectively, to our knowledge, our data demonstrate for the first time the restoration of peripheral blood NK cell cytokine production and cytotoxicity in PWO treated with GLP-1 analogues. The restoration appears to be in a weight loss-independent manner,” they concluded. “We provide evidence that the restoration in cytokine production is linked to improved cellular metabolism. The direct restoration, by GLP-1 therapy, of NK cell cytokine production and metabolism in PWO may be contributing to the overall benefits being seen with this class of medication.”
"We are finally reaching the point where medical treatments for the disease of obesity are being shown to prevent the complications of having obesity,” said Professor Donal O'Shea, HSE National Lead for Obesity & Principal Investigator. “The current findings represent very positive news for people living with obesity on GLP-1 therapy and suggest the benefits of this family of treatments may extend to a reduction in cancer risk."
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