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05 Dec 2023 — New research shows that a long-chain fatty acid — trans vaccinic acid (TVA) — found in meat and dairy products enhances immune cell function and anti-tumor immunity in vivo. Rather than recommending that people increase their intake of red meat and dairy because that has been linked to adverse health effects, the researchers suggest that the nutrient could complement clinical cancer treatment.
Patients with higher levels of TVA 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 by-products, while the rest circulates in the blood.
“As a natural food component, TVA has high translational potential for use as a dietary element or treatment supplement in therapeutic approaches to improve clinical outcomes,” senior author Jing Chen, Ph.D., professor of medicine at the University of Chicago , tells Nutrition Insights.
“For example, combinations of TVA inhibitors and immune checkpoints could be tested for improved immunotherapies to treat cancer patients. TVA can be combined with specific T-cell agents such as Blinatumomab to treat B-ALL patients, or with CAR T cells for improved efficacy in the treatment of cancer patients.”
In addition, it suggests that TVA supplementation may improve the immune system’s response to infections, and may lower circulating triglycerides in the blood.
The researchers note that although TVA is the most abundant trans fatty acid in human milk, the body cannot produce it independently.
TVA supplementation may also improve the immune systems response to infections.Blood nutrient compound screening
Although there is extensive research into links 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 on the nutrients and metabolites derived from food, we start to see how they affect physiology and pathology,” he explains. “By targeting 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 constructed a blood nutrient compound library of 235 nutrient-derived bioactive molecules.
For the study published in naturethe researchers 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 and mouse cells. Since a large portion is still circulating in the blood, Chen notes that this “must be doing something else.”
“After millions of years of evolution, there are only a few hundred metabolites derived from food that circulate in the blood, which means they may have some importance in our biology,” he said.
“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 level of the whole organism – that’s amazing and fascinating.”
Tumor experiments
When the research team fed mice on a diet enriched with TVA, this 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 tumor-infiltrating CD8+ T cells.
The researchers also determined how TVA affects T cells through molecular and genetic analyses.
TVA inactivates a receptor on the cell surface, which is commonly activated by short-chain fatty acids produced by gut microbiota. The nutrient overpowers these acids to initiate 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, regulating gene expression. This process affects important cellular functions that affect growth, metabolism, learning and memory, among others.
Taking supplements with enriched bioactive nutrients is likely to be more effective than eating foods that contain these nutrients.When the researchers removed this receptor from the CD8+ T cells, they lost their enhanced ability to fight tumors.
By analyzing blood samples from patients undergoing immunotherapy treatment for lymphoma, the researchers found that, in general, people with higher TVA levels responded better to treatment. They found similar results when testing cell lines from leukemia.
supplement a balanced diet
At the same time, the researchers emphasize that there is increasing evidence of the harmful health effects of eating too much red meat and dairy.
“Our findings suggest that a balanced diet probably good for health. “It may be more important to focus on the bioactivity of nutrients rather than individual foods, and taking supplements with enriched bioactive nutrients is likely to be more effective than eating foods that contain these nutrients,” warns Chen.
In addition, he says, early data show that other plant fatty acids signal to a TVA-like receptor. “We believe there is a strong possibility that plant nutrients can do the same thing by activating the CREB pathway.”
As the new research highlights the promise of a metabolic approach to understanding how dietary building blocks affect 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 biological processes such as ageing.
“There’s still a lot we don’t know. For example, a comprehensive understanding of the different physiological and pathological functions of each nutrient from different foods is not yet available. More comprehensive studies are needed in the future to clarify the functions of these nutrients.”
By Jolanda van Hal
This feature is provided by Food Ingredients Firstsister website, Nutrition Insights.
To contact our editorial team please email us at editorial@cnsmedia.com
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