Trans-vaccenic acid in red meat and dairy enhances anti-tumor immunity, research reveals

05 Dec 2023 --- New research reveals that a long-chain fatty acid — trans-vaccenic acid (TVA) — found in meat and dairy products enhances immune cell function and anti-tumor immunity in vivo. Rather than suggesting people increase their red meat and dairy intake as that has been linked to detrimental health effects, the researchers indicate that the nutrient can potentially complement clinical cancer treatment.

Patients with higher levels of TVA in their blood also responded better to immunotherapy. Around 20% of the nutrient — found in beef, lamb and dairy products such as milk and butter — is broken down into byproducts, with the remainder circulating in the blood. 

“As a natural food component, TVA has high translational potential to be used as a dietary element or a treatment supplement in therapeutic approaches to ameliorate clinical outcomes,” senior author Jing Chen, Ph.D., professor of medicine at the University of Chicago, tells Nutrition 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 improved efficacy of treating cancer patients.”

In addition, he suggests that TVA supplementation might enhance the immune system response to infections, and it may lower circulating triglycerides in the blood.

The researchers note that while TVA is the most abundant trans fatty acid in human milk, the body cannot produce it independently. 

TVA supplementation may also enhance the immune systems’ response to infections.Blood nutrient compound screening 
While there is extensive research on links between diet and human health, Chen notes that it is difficult to understand the underlying mechanisms due to the variety of foods people eat. 

“But if we focus on just the nutrients and metabolites derived from food, we begin to see how they influence physiology and pathology,” he explains. “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 that circulate in the blood influence cancer development and response to disease treatment, the researchers built a blood nutrient compound library with 235 bioactive molecules derived from nutrients. 

For the study published in Nature, the researchers screened the compounds in this library for their ability to activate CD8+ T cells — critical for killing cancerous cells. 

The scientists discovered that TVA performed the best in human and mouse cells. As a large share remains circulating in the blood, Chen notes that this means “there must be something else it does.” 

“After millions of years of evolution, there are only a couple hundred metabolites derived from food that end up circulating in the blood, so that means they could have some importance in our biology,” he highlights. 

“To see that a single nutrient like TVA has a very 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, 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 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, commonly activated by short-chain fatty acids produced by gut microbiota. The nutrient overpowers these acids to start a signaling process known as the CREB (Cyclic adenosine monophosphate response element-binding protein) pathway. 

The CREB pathway activates when certain signals stimulate a cell. This activates CREB, which then binds to DNA, regulating gene expression. This process influences important cellular functions that influence growth, metabolism, learning and memory, among others.

Taking supplements with enriched bioactive nutrients is likely more efficient than consuming foods containing these nutrients.When the researchers removed this receptor from the CD8+ T cells, they lost their improved tumor-fighting ability. 

By analyzing blood samples from patients undergoing immunotherapy treatment for lymphoma, the researchers find that, in general, people with higher TVA levels responded better to treatment. They found similar results when testing cell lines from leukemia. 

Supplementing a balanced diet  
At the same time, the researchers stress that there is a growing body of evidence on the detrimental health effects of consuming too much red meat and dairy.  

“Our results suggest that a balanced diet is probably good for health. Focusing on the bioactivity of nutrients rather than individual food might be more important, and taking supplements with enriched bioactive nutrients is likely more efficient than consuming foods containing these nutrients,” cautions Chen. 

Moreover, he adds that early data indicates that other plant fatty acids signal a receptor similar to TVA. “We believe there is a high possibility that plant nutrients can do the same thing by activating the CREB pathway.”

As the new research highlights the promise of a metabolomic approach to understanding how diet’s 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 aging. 

“There are still many things that we don’t know. For example, a comprehensive understanding of the diverse physiological and pathological functions of each nutrient from different foods is still unavailable. This warrants future more comprehensive studies to elucidate these functions of nutrients.” 

By Jolanda van Hal