December 5, 2023 — New research shows that a long-chain fatty acid – trans-vaccenic acid (TVA) – found in meat and dairy products improves immune cell function and anti-tumor immunity in vivo. Rather than suggesting people increase their intake of red meat and dairy, as this has been linked to adverse health effects, the researchers indicate that the nutrient could potentially complement clinical cancer treatment.
Patients with higher TVA levels in their blood also responded better to immunotherapy. About 20% of the nutrient – found in beef, lamb and dairy products such as milk and butter – is broken down into byproducts, while the rest circulates in the blood.
“As a natural nutritional component, TVA has high translational potential to be used as a nutritional element or as a treatment supplement in therapeutic approaches to improve clinical outcomes,” senior author Jing Chen, Ph.D., professor of medicine at the University of Chicago, says. Nutritional insight.
“For example, a combination of TVA and immune checkpoint inhibitors could be tested for improved immunotherapies to treat cancer patients. TVA can be combined with specific T cell engagers such as Blinatumomab to treat B-ALL patients, or with CAR T cells for better efficacy in treating cancer patients.”
Furthermore, he suggests that TVA supplementation could enhance the immune system’s response to infections and that it could lower circulating triglycerides in the blood.
The researchers note that although TVA is the most abundant trans fatty acid in breast milk, the body cannot produce it on its own.
TVA supplementation may also boost the immune system’s response to infections.Screening of nutrients in the blood
Although there has been extensive research into the link between diet and human health, Chen notes that understanding the underlying mechanisms is difficult due to the variety of foods people eat.
“But if we focus only on the nutrients and metabolites that come from food, we start to see how these influence physiology and pathology,” he explains. “By focusing on nutrients that can activate T-cell responses, we found one that enhances anti-tumor immunity by activating an important immune pathway.”
To understand how metabolites, nutrients and other molecules circulating in the blood influence cancer development and response to disease treatment, the researchers compiled a blood nutrient library of 235 bioactive molecules derived from nutrients.
For the research published in Natureresearchers screened the compounds in this library for their ability to activate CD8+ T cells – crucial for killing cancer cells.
The scientists found that TVA performed best in human cells and mouse cells. Because much of it continues to circulate in the blood, Chen notes that this means “there must be something else.”
“After millions of years of evolution, there are only a few hundred metabolites derived from food that ultimately circulate in the blood, so that means they could be of some importance in our biology,” he points out.
“To see that a single nutrient like TVA has a highly targeted mechanism on a targeted immune cell type, with a profound physiological response at the whole organism level – I find that amazing and intriguing.”
Tumor experiments
When the research team fed mice a diet enriched with TVA, it significantly reduced the tumor growth potential of melanoma and colon cancer cells compared to mice on a control diet. The TVA-enriched diet also enhanced the ability of CD8+ T cells to infiltrate tumors.
The researchers also determined how TVA affects T cells through molecular and genetic analyses.
TVA inactivates a receptor on the cell surface, normally activated by short-chain fatty acids produced by the gut microbiota. The nutrient overpowers these acids and starts a signaling process known as the CREB (Cyclic adenosine monophosphate response element-binding protein) pathway.
The CREB pathway is activated when certain signals stimulate a cell. This activates CREB, which then binds to DNA and regulates gene expression. This process affects important cellular functions that include growth, metabolism, learning and memory.
Taking supplements with enriched bioactive nutrients is likely to be more efficient than consuming foods containing these nutrients.When the researchers removed this receptor from the CD8+ T cells, they lost their enhanced tumor-fighting ability.
By analyzing blood samples from patients undergoing immunotherapy treatment for lymphoma, researchers found that people with higher TVA levels generally responded better to treatment. They found similar results when testing cell lines against leukemia.
Supplement to a balanced diet
At the same time, the researchers emphasize that there is growing evidence about the harmful health effects of consuming too much red meat and dairy products.
“Our results suggest that a balanced diet is probably good for your health. It may be more important to focus on the bioactivity of nutrients rather than individual foods, and taking supplements with fortified bioactive nutrients is likely more efficient than consuming foods containing these nutrients,” Chen warns.
Additionally, he adds that early data indicate that other plant fatty acids signal a receptor similar to TVA. “We believe there is a good chance that plant nutrients can do the same by activating the CREB pathway.”
While the new research highlights the promise of a metabolomic approach to understanding how the building blocks of diet influence health, Chen adds that the research team hopes to build a library of nutrients circulating in the blood to understand their impact on immunity and understand biological processes such as aging.
“There are still many things we don’t know. For example, a comprehensive understanding of the diverse physiological and pathological functions of each nutrient from different foods is still not available. This warrants future, more extensive studies to elucidate these nutrient functions.”
By Jolanda van Hal
This feature is provided by Food ingredients first‘s sister website, Nutritional insight.
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