A nutrient from red meat and dairy improves the immune response against cancer

In medicine, sometimes the bad guys are not so bad and the good guys are not so good. It often has to do with the amounts, the timing or even the ability to separate the wheat from the chaff. Chemotherapy, for example, one of the most effective cancer treatments, was the byproduct of mustard gas, which is a biological weapon; vitamin A, on the other hand, is an essential substance for the formation and maintenance of soft tissues and bones and has antioxidant properties, but in excess it can cause skin problems, bone weakness and joint pain.

Nuances always matter. This is proved once again by research published this week in the journal Nature, which concludes that red meat — a food that nutrition experts recommend limiting as much as possible — contains a nutrient that improves the immune response against cancer. After conducting studies with animal models and human cells, the researchers came to the conclusion that trans-vaccenic acid, a trans fatty acid found in beef, milk and butter, has potential as a dietary supplement to optimize the impact of immunotherapy in oncology. Still, experts recommend exercising caution when interpreting the results.

A group of researchers from the University of Chicago focused on the nutrients circulating in the blood, approximately 700 substances including organic metabolites, lipids and proteins, that could play a role in health and disease. “There are still many things we don’t know yet. A comprehensive understanding of diverse physiological and pathological functions of each nutrient from different foods is still not available. Our study attempted to address this dilemma,” says study author Jing Chen, professor in the Department of Medicine and director of the Cancer Metabolomics Research Center at the University of Chicago.

The scientists reviewed a sort of library with more than 200 diet-derived nutrients that circulate in the blood, and studied which ones could have a role or influence anti-tumor immunity. Their research revealed that a particular trans fat, trans-vaccenic acid (TVA), promoted the ability of a type of immune system cell (CD8+ T cells) to infiltrate tumors and kill malignant cells. “Only around 19% or 12% of dietary TVA can be converted to rumenic acid by humans or mice, respectively, so TVA is not a typical nutrient for energy or as a biosynthetic building block for macromolecules. Our study shows that TVA has regulatory functions,” points out Chen.

The experiments with mice showed that a diet enriched with this trans fat reduced the expansion capacity of melanoma and colon cancer tumor cells, compared to those animals fed with control diet. The research also revealed that a TVA-enriched diet helps CD8+ T cells infiltrate tumors better. “Our studies in mouse models show TVA’s anti-tumor activity through the improvement of the CD8+ T cell function. This justifies future clinical studies that use TVA as an adjunct to treatment for T cell-based immunotherapies,” explains Chen.

The scientists also tested what happened when some treatments were combined with this nutrient, and found that dietary TVA added to a type of immunotherapy “showed synergistic attenuation of tumor growth.” In another retrospective clinical study, the authors noticed that patients with lymphoma who had higher levels of TVA responded better to CAR-T, another type of immunotherapy that consists in extracting T lymphocytes from patients to improve them in the laboratory so that they better recognize and kill cancer cells, and then re-injecting them into their body. “These findings align with the notion that dietary TVA may improve clinical responsiveness to T cell-based immunotherapies,” the researchers suggest.

According to the authors, this study opens the door to further closely inspecting the potential roles of circulating nutrients in human health and disease. In the case of TVA, they add, there are epidemiological studies that suggest that circulating levels of this trans fatty acid in humans are associated with lower adiposity, diabetes risk and systemic inflammation, although its effects on the risk of cancer and cardiovascular diseases are unclear. Chen admits that they still don’t know whether this nutrient can be harmful in other contexts or for other ailments, but insists: “TVA is not a bad trans fatty acid, because previous studies have shown that in models of dyslipidemia [abnormal levels of fats in the blood] in rodents, the TVA-enriched diet has hypolipidemic effects by reducing circulating triglycerides.”

Focusing on the nutrient, not the food

However, Chen and his team emphasize that a comprehensive understanding of the interactive and collective influences of diverse dietary nutrients on cancer risk, development and therapy responses is crucial for diet choices. “Consuming red meat may provide TVA for improved anti-tumor immunity, but a high intake of red meat has been positively associated with risk of many cancers, including breast, colorectal, colon and rectal cancer,” they write. The authors clarify, in fact, that what their studies support is “TVA supplementation as a more targeted and efficient way than dietary changes to benefit anti-tumor immunity.”

“Our results suggest that a balanced diet is probably good for your health. Focusing on bioactivity of nutrients rather than individual food might be more important, and taking supplements with enriched bioactive nutrients is likely more efficient than consuming foods containing these nutrients,” Chen says. The scientist assures that “as a natural food component, TVA has high translational potential as a dietary element in therapeutic approaches to improve clinical outcomes of diverse anti-cancer therapies.” He cites several examples: “A combination of TVA and immune checkpoint inhibitors could be tested to improve immunotherapies to treat cancer patients. TVA can be combined with specific T-cell activators like [the drug] blinatumomab, to treat patients with B-cell acute lymphoblastic leukemia, or with CAR-T cells to improve efficacy in the treatment of cancer patients.”

Miguel Quintela, director of the Clinical Research Program of the Spanish National Cancer Research Center (CNIO) and head of a spin-off of personalized oncological nutrition (TCNterapia), warns that, although this study is “a very important first observation,” it is too soon to start issuing recommendations. “I cannot suggest my cancer patients to eat a steak. An experimental demonstration is one thing, and another is to see, in the long term, whether it actually increases or decreases a disease.” The oncologist admits that the results of the research, in which he did not participate, seem “robust,” but it is necessary to know how to interpret and contextualize them. “Right now, you can’t make a list of pure nutrients and eat nothing but that. Each nutrient comes in foods of complex composition. The final consumer cannot isolate that nutrient from the meat. Still, this study opens up more fields of study.”

What this research does represent, in Quintela’s opinion, is a boost to precision nutrition. “We need to be much more precise,” he says. “[TVA] is a saturated fatty acid, which nutrition experts tell us not to eat, and by itself it has lipid-lowering, anti-inflammatory, anti-diabetogenic and anti-tumor capacities, promoting the anti-tumor immune response. In other words, it is a trans fatty acid that is beneficial to health.” The oncologist adds a final reflection: “At the end of the day, a food is made up of hundreds of different molecules. Overall, the effect of red meat is probably bad, as proved by many epidemiological studies. But that doesn’t mean that it doesn’t have specific nutrients that exert positive functions. Hence the need to make a precision approach, beyond the generalizations that one hears everywhere.”

Above all, prudence

Antoni Agudo, head of the Nutrition and Cancer Unit of the Catalan Institute of Oncology, thinks that the study, in which he did not participate, is “very well documented,” but appeals for “prudence” when interpreting the results. “TVA is shown to have a fairly specific effect, which is the reprogramming of CD8+ T cells to activate immunity. But the immune system has many pathways of action and this is just one of them. This means that it may have potential in some types of tumors or in people who are following a specific treatment, but not in all cases of cancer.”

Furthermore, Agudo emphasizes, these findings are described “in animal experimental models and in human cells in vitro.” “It’s a long way from the effects being seen in animals to them having an impact – if ever – in clinical practice.”

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