Meat and dairy nutrient helps fight cancer, find researchers

TVA has a ‘very targeted’ mechanism​

TVA is a long-chain fatty acid found in meat and dairy products from grazing animals such as cows and sheep. The fatty acid is also present in human milk, but the body cannot produce it on its own.

TVA was just one nutrient tested by scientists to see how it influences cancer development and responds to cancer treatments.

After first assembling a ‘blood nutrient’ compound library consisting of 255 bioactive molecules derived from nutrients, researchers screened these compounds to test their ability to influence anti-tumour immunity by activating CD8+ T cells – a group of immune cells critical for killing cancerous or virally infected cells.

Using both human and mouse cells, the six most effective compounds were selected. And of those six, it was found that TVA performed the best.

“By focusing on nutrients that can activate T cell responses, we found one that actually enhances anti-tumour immunity by activating an important immune pathway,” ​explained Jing Chen, the Janet Davison Rowley Distinguished Service Professor of Medicine at the University of Chicago and one of the senior authors.

Interestingly, in the body only about 20% of TVA is broken down into other by-products. The other 80% is left to circulate in the blood, which Chen suggested might mean it has another function.

“To see that a single nutrient like TVA has a very targeted mechanism on a targeted immune cell type…I find that really amazing and intriguing.”​

Potential to help humans battling cancer?​

To get a better understanding of TVA’s potential, the scientists conducted experiments with cells and mouse models of diverse tumour types. When mice were fed a diet enriched with TVA, tumour growth potential significantly reduced for two particular cancers types: melanoma and colon cancer. Compared to mice fed a control diet, the TVA diet also enhanced the ability of CD8+ T cells to infiltrate tumours.

Molecular and genetic analyses were conducted to try to understand exactly how TVA was affecting the T cells. It was found TVA inactivates a receptor on the cell surface called GPR43 which is usually activated by short-chain fatty acids often produced by gut microbiota.

According to the research team, TVA overpowers these short-chain fatty acids and activates a cellular signalling process called the CREB pathway. When the GPR43 receptor was removed from CD8+ T cells in mouse models, the improved tumour-fighting ability was lost.

To investigate how whether TVA has the potential to benefit humans battling cancer, the research team analysed blood samples from patients being treated with CAR-T cell immunotherapy for lymphoma. Patients that tended to respond to treatment better also had higher levels of TVA in their blood.

Testing cell lines from leukaemia revealed that TVA enhanced the ability of an immunotherapy drug to kill leukaemia cells.

Not an excuse to eat more burgers and ice cream​

Before meat and dairy lovers start salivating at the idea of eating more with health in mind, the findings are not an excuse to consume more burgers and ice cream. Rather, the study suggests that TVA could be used as a dietary supplement – rather than a food source – to help various T cell-based cancer treatments.

Chen also suggested that other nutrients may have similar benefits. “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.”​

In the future, the scientific team hopes to build a comprehensive library of nutrients circulating in the blood – just like TVA – to better understand their impact on things like immunity and ageing. “After millions of years of evolution, there are only a couple of hundred metabolites derived from food that end up circulating in the blood, so that means they could have some importance in our biology,” ​said Chen.

Source: Nature​
‘Trans-vaccenic acid reprograms CD8+ T cells and anti-tumour immunity’
Published 22 November 2023
DOI: https://doi.org/10.1038/s41586-023-06749-3
Authors: Fat, H., Xia, S., Xiang, J. et al.