It is becoming increasingly clear in science that food is not just fuel. What we eat is not only converted into energy or stored as nutrients, but also becomes part of the molecular language through which our body regulates itself. And in some cases, that language can directly influence how our immune system responds to something as complex as cancer.
A recent study published in Nature has taken this idea to a much more concrete level. Researchers identified a specific molecule, a fatty acid called trans-vaccenic acid (TVA), naturally present in foods such as beef, lamb, and dairy products, which can directly enhance the immune system’s ability to fight tumors. But what is most interesting is not only the molecule itself, but what it represents: a direct mechanistic connection between diet and immune function in cancer.
This finding was not accidental. Researchers conducted a large-scale analysis of more than 600 nutritional compounds present in human blood, searching for those capable of influencing immune cells. Among all of them, TVA clearly stood out. It showed a consistent ability to reprogram CD8+ T cells, which are the main cells responsible for recognizing and destroying cancer cells.
To understand why this is important, it is necessary to consider the challenge these cells face. CD8+ T cells are extremely effective when fully activated. They can identify abnormal cells, attack them with precision, and eliminate them. However, tumors are not passive. They create an environment that suppresses immune system activity, driving these cells into a state of “exhaustion,” where they lose their functional capacity.
This is where TVA comes into play.
Instead of directly attacking the tumor, this molecule modifies the behavior of the immune system. It acts as a kind of molecular switch that improves the functional state of CD8+ T cells, helping them regain their activity and perform their role more effectively. This is what the authors describe as “extrinsic reprogramming” of immune cells — in other words, an external factor (diet) that changes how they function.
The mechanism behind this effect is particularly interesting. TVA interacts with a receptor on the surface of T cells called GPR43. This receptor normally responds to short-chain fatty acids produced by the gut microbiota and plays a regulatory role in the immune system.
But TVA acts differently: instead of activating this receptor, it blocks it.
By acting as an antagonist of GPR43, TVA prevents its usual signaling. This triggers a cascade of events inside the cell, activating a signaling pathway known as the cAMP–PKA–CREB axis, which regulates gene expression and cellular activation.
Once this pathway is activated, several important effects occur. Cells begin to express genes related to proliferation and activation, meaning they become more numerous and more functional. At the same time, genes associated with cellular exhaustion are reduced.
Figure 1. Trans-vaccenic acid (TVA), a fatty acid naturally present in foods from ruminant animals, has been shown to enhance the activity of CD8⁺ T cells by modulating their signaling pathways. By interfering with regulatory signals at the cell surface, TVA promotes intracellular processes that strengthen immune responses, allowing these cells to more effectively target and eliminate tumor cells.
In practical terms, this translates into T cells that produce more cytokines (key immune signaling molecules) and have a greater ability to destroy tumor cells.
An especially interesting aspect of the study is that TVA does not primarily act as an energy source for cells. Unlike other fatty acids, it is not significantly used in the energy metabolism of T cells. Instead, it functions as a signaling molecule that changes their programming at the genetic level.
From a clinical perspective, the implications are promising, but they must be interpreted with caution. This study suggests that certain components of the diet can modulate the immune system in the context of cancer. However, this does not mean that consuming foods rich in TVA cures cancer.
In fact, one of the most interesting aspects is its potential synergy with existing immunotherapies. Treatments such as immune checkpoint inhibitors remove inhibitory signals from the immune system, while TVA enhances its activation. Together, they could generate a more effective response.
Still, many questions remain. Most of the data come from preclinical models. It is not yet known what the effective dose would be in humans, how it is distributed in tissues, or how factors such as metabolism or chronic inflammation influence its activity.
Nor is it fully understood how TVA structurally interacts with the GPR43 receptor. Solving this could allow the development of new therapeutic molecules based on this mechanism.
Because in the end, the immune system is not separate from what we eat. It is in constant interaction with it. And as this study shows, it can sometimes even be guided by it.
Main reference:
Fan, H., Xia, S., Xiang, J., Li, Y., Ross, M. O., Lim, S. A., Yang, F., Tu, J., Xie, L., Dougherty, U., Zhang, F. Q., Zheng, Z., Zhang, R., Wu, R., Dong, L., Su, R., Chen, X., Althaus, T., Riedell, P. A., Jonker, P. B., … Chen, J. (2023). Trans-vaccenic acid reprograms CD8+ T cells and anti-tumour immunity. Nature, 623(7989), 1034–1043. https://doi.org/10.1038/s41586-023-06749-3
Other references:
Te Morenga, L., & Montez, J. M. (2017). Health effects of saturated and trans-fatty acid intake in children and adolescents: Systematic review and meta-analysis. PloS one, 12(11), e0186672. https://doi.org/10.1371/journal.pone.0186672
Sommerfeld M. (1983). Trans unsaturated fatty acids in natural products and processed foods. Progress in lipid research, 22(3), 221–233. https://doi.org/10.1016/0163-7827(83)90010-3
Turpeinen, A. M., Mutanen, M., Aro, A., Salminen, I., Basu, S., Palmquist, D. L., & Griinari, J. M. (2002). Bioconversion of vaccenic acid to conjugated linoleic acid in humans. The American journal of clinical nutrition, 76(3), 504–510. https://doi.org/10.1093/ajcn/76.3.504
