July 23, 2024

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Fatty Acids in Beef and Dairy Enhance Immune Cell Cancer Response

Research Reveals Fatty Acids in Beef and Dairy Enhance Immune Cell Cancer Response

Research Reveals Fatty Acids in Beef and Dairy Enhance Immune Cell Cancer Response

A new study has found that trans-palmitoleic acid, a fatty acid present in dairy and grass-fed animal meat, may enhance the anti-cancer capabilities of the immune system’s T cells.

This nutrient has also been discovered to boost the effectiveness of immunotherapy, potentially serving as a nutritional supplement for cancer treatment.

Diet has been proven to offer a range of health benefits, including preventing cancer spread or enhancing disease treatment.

However, due to the diversity of food and the complexity of dietary metabolism, little is known about how specific nutrients affect physiological and pathological processes in the human body.

Research Reveals Fatty Acids in Beef and Dairy Enhance Immune Cell Cancer Response

Researchers at the University of Chicago addressed this challenge by constructing a blood nutrient compound library and screening its contents to identify nutrients influencing cancer development and treatment response.

“There have been many studies attempting to decipher the connection between diet and human health, but due to the wide variety of foods people consume, it’s challenging to understand their underlying mechanisms,” said the lead author of the study, Jing Chen. “However, by focusing on nutrients and metabolites extracted from food, we begin to see how they impact physiology and pathology.”

The researchers’ library included 255 bioactive nutrient-derived molecules, which they screened to assess their ability to influence the anti-tumor activity of CD8+ T cells, the effector cells responsible for killing cancer cells or cells infected with pathogens. Among their “top six,” trans-palmitoleic acid (TVA) was identified as the most promising.

“By focusing on nutrients capable of activating T cell responses, we’ve discovered a substance that can actually enhance anti-tumor immunity by activating crucial immune pathways,” Chen explained.

TVA is a natural trans-fatty acid primarily found in the fat of ruminant animals like cattle and sheep, as well as in dairy products like milk and butter. The human body cannot produce it on its own. Interestingly, the name TVA is derived from Latin, meaning “cow” or “vacca.” Only about 20% of TVA is broken down into other by-products, with the remaining 80% circulating in the bloodstream. “This implies it surely has other functions, so we began to study it more,” Chen said.

Through experiments on cells of different tumor types and mouse models, the researchers found that feeding mice a diet rich in TVA significantly reduced the tumor growth potential of melanoma and colon cancer cells compared to mice on a control diet. The TVA-rich diet led to an increase in CD8+ T cells in tumor-infiltrating lymphocytes (TILs), which recognize cancer cells as abnormal and penetrate the tumor microenvironment to kill them. Dietary TVA reduced the exhaustion of CD8+ T cells in tumors and promoted cell function, including survival. A TVA diet did not affect CD8+ T cell populations and function in tumor-free mice, suggesting that the impact of dietary TVA on T cells may depend on generating an immune response.

The researchers conducted molecular and genetic analyses to determine the effects of TVA on T cells, including a new technology called Ketone Aldehyde-Assisted Single-Stranded DNA Sequencing (KAS-seq) that monitors single-stranded DNA transcription. The analysis indicated that TVA deactivated the surface receptor GPR43 on immune cells, which is typically activated by short-chain fatty acids produced by the gut microbiota. TVA overwhelmed short-chain fatty acids, activating the CREB pathway, a cell signaling pathway involving various functions such as cell growth, survival, and differentiation. The researchers also found that mouse models lacking the GPR43 receptor in CD8+ T cells lacked enhanced anti-tumor capabilities.

The final step of the study involved analyzing blood samples from patients undergoing chimeric antigen receptor T-cell (CAR-T) lymphoma immunotherapy. CAR-T cell therapy uses genetically modified T cells to more effectively target and destroy cancer cells. The researchers found that patients with higher levels of TVA tended to have better treatment responses than those with lower levels. They also tested leukemia cell lines and found that TVA enhanced the ability of blinatumomab, an immunotherapy drug acting on T cells, to kill leukemia cells.

The study results suggest that TVA could be used as a dietary supplement to enhance the effectiveness of T cell-based cancer treatment. However, the researchers quickly pointed out that the importance lies in the nutrient itself, not its food source, and advised against consuming excessive amounts of red meat and dairy to elevate TVA levels, which could be detrimental to health.

This research underscores the importance of the emerging field of metabolomics (the large-scale study of cell metabolites) in understanding how our dietary structure influences our health.

“After millions of years of evolution, only a few hundred metabolites from food ultimately circulate in the blood, so this suggests they may have some importance in our biology,” Chen said. “Seeing a single nutrient like TVA have such targeted mechanisms on specific immune cell types, producing profound physiological responses at the whole organism level—I find that truly fascinating and intriguing.”

The study was published in the journal Nature.

Research Reveals Fatty Acids in Beef and Dairy Enhance Immune Cell Cancer Response

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