International Business Department           Liu Bojia           November 29, 2023

  We consume different types of food every day, from starchy staples, to protein-rich meats, to dietary fibre-rich fruits, vegetables and coarse grains. The variety of nutrients from food not only ensures the functioning of the human body, but also shapes the foundation of human physiology.

  Some studies have previously found that as the structure of the human diet changes, human physiology and pathology evolve adaptively, suggesting that the nutrient content of food affects our physiological processes.

  In a recent study in Nature, Professor Chuan He and Professor Jing Chen from the University of Chicago, in collaboration with Professor Hongbo Chi from St. Jude Children's Research Hospital, found that trans-isoleic acid (TVA) in food allowed more T-cells to infiltrate the tumour area and enhanced the cancer-killing ability of CD8+ T-cells. Those with higher levels of TVA in their blood also responded better to immunotherapy.

  TVA is a long-chain fatty acid found in large quantities in the meat of ruminants, including beef and lamb, while dairy products also contain much TVA. in addition to beef and lamb, TVA is also found in human breast milk, where it is one of the most abundant types of trans fatty acids. And when TVA enters the body, about 20 per cent is broken down into by-products, with most of the rest remaining in the circulatory system, suggesting that this nutrient rightly has its own special role to play.

  Confirming the specific role of TVA isn't simple, though. To address this question, the research team built a molecular library of 235 nutrients based on more than 600 food nutrients, including inorganic compounds, organic metabolites, lipids, proteins, and dietary supplement molecules, which travel throughout the body with the circulatory system as soon as they are broken down from food.

  Among the many targets of action, the research team focused on one point: which molecular compounds activate CD8+ T cells? The results showed that of all the compounds, TVA was the most effective in activating T cells and in inducing them to produce interleukin 2. In addition to this, TVA was able to reverse T cell exhaustion when T cells were co-cultured with cancer cells. However, if TVA was cultured with cancer cells alone, it was unable to cause apoptosis in cancer cells, which also suggests that TVA achieves its anti-cancer effect through T cells.

  In a follow-up experiment, the authors also constructed a batch of tumour model mice, and then gave them either normal chow, or chow with extra TVA, respectively. The results were clear: the mice that consumed the TVA-containing chow had slower growth rates and smaller tumour sizes of melanoma and colon cancer cells compared to the control group.

  The authors analysed these tumours and found that consumption of the TVA-containing chow resulted in a high number of CD8+ T-cells in the tumours, in addition to an increase in the number of neutrophils and monocytes, changes that were not seen in the regular chow group.

  In terms of molecular mechanism, TVA inactivates the GPR43 receptor on the cell surface, which originally pairs with short-chain fatty acids produced by microbial breakdown of food. However, after TVA inactivates it, it stimulates another cAMP-related signalling pathway that promotes the function of CD8+ T cells.

  The authors suggest that TVA may be able to be an adjunctive nutrient to cancer treatment, boosting the effectiveness of immunotherapy. But we don't have to consume extra large amounts of meat for this purpose; after all, excessive red meat intake may also have negative health effects. The paper also points out that previous studies have found that excessive red meat intake is associated with an elevated risk of a number of cancers, including breast and colorectal cancer. Therefore, in the future, supplementing TVA in the form of supplements and the like may be a more sensible way to boost T-cell function.