Beef and dairy contain a powerful cancer-fighting nutrient

A nutrient found in beef and dairy products enhances the immune system’s response to cancer, according to a new study from the University of Chicago. The researchers identified trans-vaccenic acid (TVA), a long-chain fatty acid, as a key player in improving the effectiveness of CD8+ T cells in fighting cancer cells.

The study represents a major step forward in understanding the complex relationship between diet and health, particularly in the context of cancer treatment.

Immune response 

TVA is a long-chain fatty acid prevalent in meat and dairy from grazing animals like cows and sheep. The experts determined that TVA improves the infiltration and cancer cell-killing capabilities of CD8+ T cells, crucial players in the body’s immune response. 

The research revealed that patients with higher levels of TVA circulating in the blood responded better to immunotherapy, indicating this nutrient’s potential as a dietary supplement to augment cancer treatment.

Link between diet and health 

“There are many studies trying to decipher the link between diet and human health, and it’s very difficult to understand the underlying mechanisms because of the wide 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,” said study senior author Dr. Jing Chen.

“By focusing on nutrients that can activate T cell responses, we found one that actually enhances anti-tumor immunity by activating an important immune pathway.”

Focus of the study 

The study began with a comprehensive analysis of about 700 known metabolites derived from food. The researchers developed a “blood nutrient” compound library of 235 bioactive molecules from these metabolites. 

This library was used to identify compounds that could activate anti-tumor immunity by stimulating CD8+ T cells, and TVA emerged as a top candidate. 

While TVA is abundant in human milk, the body cannot produce it independently. Approximately 80% of ingested TVA remains in the blood, suggesting other significant roles for this nutrient.

Critical insights 

The researchers discovered that TVA intake notably reduced tumor growth in mice and enhanced CD8+ T cells’ tumor infiltration. 

Advanced molecular and genetic analyses, including a novel technique called kethoxal-assisted single-stranded DNA sequencing (KAS-seq), revealed that TVA inactivates the GPR43 receptor, which is typically triggered by short-chain fatty acids from gut microbiota. This inactivation leads to the activation of the CREB pathway, vital for various cellular functions.

Cancer treatment

The experts collaborated with other UChicago experts to examine TVA’s effects on patients undergoing CAR-T cell immunotherapy for lymphoma and leukemia cell lines. 

Patients with higher TVA levels responded more favorably to treatment, and TVA also enhanced the efficacy of an immunotherapy drug against leukemia cells.

Study implications

Despite the health risks associated with excessive red meat and dairy consumption, this study suggests that TVA supplements could promote T cell activity in cancer treatments. 

Dr. Chen noted that it is important to determine the optimized amount of the nutrient itself, not the food source.

“There is early data showing that other fatty acids from plants signal through a similar receptor, so we believe there is a high possibility that nutrients from plants can do the same thing by activating the CREB pathway as well,” said Dr. Chen.

Metabolites 

The study underscores the potential of a metabolomic approach in understanding how dietary components affect health. 

Dr. Chen said his team hopes to build a comprehensive library of nutrients circulating in the blood to understand their impact on immunity and other biological processes like aging.

“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,” said Dr. Chen. 

“To see that a single nutrient like TVA has a very targeted mechanism on a targeted immune cell type, with a very profound physiological response at the whole organism level – I find that really amazing and intriguing.”

The study is published in the journal Nature.

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