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  • Non-functional, naturally occurring anticancer cells may be restored by GLP-1 drugs, according to a new study.
  • The study’s authors see evidence that GLP-1 helps the cells directly and theorize that this may reduce a person’s cancer risk.
  • Obesity is associated with many forms of cancers, diabetes, hypertension, and other diseases, as well as increased mortality.
  • The anticancer cells do not work as well in people with obesity, although the mechanism behind them is still being investigated.

A new study finds that GLP-1-based weight-loss drugs directly re-activate critical cancer-fighting immune cells that have become defective due to obesity. The study’s authors assert that this occurs in addition to the cancer-preventing weight-loss effect of GLP-1 drugs.

The study finds that GLP-1 reestablished the metabolism of the body’s circulating “natural killer,” or NK, cells, restoring their ability to destroy cancer cells.

NK cells are innate immune system lymphocytes that, when healthy, are an important feature of the immune system’s quick response to a pathogen.

Previous research has found an association between obesity and impaired NK cells that are less able to kill malignant cells, leaving people with obesity exposed to a higher risk of numerous cancers.

Obesity is linked to increased mortality from cancer as well as other diseases.

“GLP-1” is an abbreviation for “glucagon-like peptide-1,” a receptor agonist that mimics the effects of the GLP-1 hormone.

Drugs based on GLP-1 help people eat less by promoting an extended sensation of being full.

For the study, the researchers sampled cells from 20 people with obesity who were already scheduled to begin weekly GLP-1 treatments of one 0.25 milligrams (mg) semaglutide injection, for 6 months.

The researchers analyzed participants’ NK cell function and metabolism using three methods: multicolor flow cytometry, enzyme-linked immunosorbent assays, and cytotoxicity assays.

After 6 months of treatment, the participants exhibited restored NK cell metabolism and function independent of GLP-1’s weight loss effect.

The study, from Maynooth University in Ireland, is published in Obesity.

While the association between obesity and NK cells has been widely reported, it is not yet entirely clear what it is about obesity that makes the cells become defective.

Dr. Mir Ali, who was not involved in the study, said that there is so far no research that definitively explains the connection. While noting that obesity increases chronic inflammation and affects cells throughout the body.

“I don’t think it’s really well understood what the effect of obesity is directly on the NK cells,” said Dr. Ali.

Dr. Andrew E. Hogan, one of the study’s principal investigators, reported that “several factors have been implicated in the dysregulation of NK cells — from leptin to fatty acids.”

“In 2018, Lydia Lynch’s lab, in collaboration with ourselves, demonstrated that fatty acids, which are elevated in obesity, directly impacted NK cell functionality. NK cells burn glucose, not fat. [So,] this was by ‘switching off’ their metabolism.”
– Dr. Andrew E. Hogan

In young, 6-year-old children with obesity, Dr. Hogan said, they also observed altered, dysregulated NK-cell metabolism.

According to Dr. Ali, all types of cancers have been linked to obesity, citing breast cancer in women, colon, pancreatic, esophageal, and rectal cancer, as well as prostate cancer in men.

“So, pretty much all across the board,” said Dr. Ali.

Dr. Ali said more research is needed to confirm a direct benefit to NK cells from GLP-1, separate from the effect of weight loss. He suggested, “It’s hard to separate the two, you know, because the patients are losing weight as well.”

Dr. Hogan explained why his team concluded these effects were “at least in part independent of weight loss.”

“In our study, not everyone lost weight, but even still, we observed improved NK cells in these people. Furthermore, we noted no link between the degree of weight loss and NK cell improvements in those who did lose weight,” he said.

Dr. Hogan added that the improvement in NK cells observed in the cell samples — where weight loss is not a factor — supports his team’s conclusion.

An obvious question the study raises is whether all people with obesity should try a GLP-1 drug to lower their risk of cancer.

For people with the condition, said Dr. Ali, “if the medication can help a patient get to a healthy weight, then yeah, definitely, it would be beneficial to them.”

“Not just for cancer risk, but [losing weight] decreases their risk for diabetes, high blood pressure, and all kinds of medical issues,” Dr. Ali added.

At the same time, Dr. Ali suggested that GLP-1 might not always be the best treatment. He felt that, “if their body mass index is high enough for surgery, then that is a better solution, because the medications have to be taken long-term to have a lasting effect.“

The current study certainly found Ozempic did not help everyone, as just nine out of the 20 participants lost a clinically significant amount of weight over the 6 months.

Dr. Ali also pointed out that NK cells are likely not all there is to obesity’s effect on cancer risk: “I think it’s a great study that again shows that obesity has wide-ranging effects [for cancer], some of which we’re beginning to understand.”

For people whose NK dysfunction is genetic and not obesity-related, Dr. Hogan predicted that GLP-1 would likely offer no benefit. Where environmental factors drive NK dysfunction, he said, “It is possible that GLP-1 could boost NK cell function. However, we have no evidence at this point, but these experiments are underway.”