by A study from the University of Chicago reveals that transvaccenic acid (TVA) in meat and dairy products increases the effectiveness of CD8+ T cells in fighting cancer. Higher TVA levels correlate with better immunotherapy responses, highlighting its potential as a complementary cancer treatment.
The scientists of the Transvaccenic acid (TVA), a long-chain fatty acid found in meat and dairy products from grass-fed animals such as cows and sheep, enhances the ability of CD8+ T cells to infiltrate tumors and kill cancer cells, according to a new study from researchers at the University of Chicago.
The research, published on November 22 in the journal Naturealso shows that patients with higher levels of circulating TVA in the blood responded better to immunotherapy, suggesting that it may have potential as a nutritional supplement to complement clinical cancer treatments.
“There are many studies trying to decipher the link between diet and human health, and it is very difficult to understand the underlying mechanisms due to the wide variety of foods people eat. But if we focus only on nutrients and metabolites derived from food, we begin to see how they influence physiology and pathology,” said Jing Chen, PhD, Janet Davison Rowley Distinguished Service Professor of Medicine at UChicago and one of the authors. main points of the new study. “By focusing on nutrients that can activate T cell responses, we found one that actually enhances antitumor immunity by activating an important immune pathway.”
Research by Jing Chen, Chuan He and their team suggests that TVA could have potential as a nutritional supplement to complement clinical cancer treatments. Credit: Rita Elena Serda, Duncan Comprehensive Cancer Center at Baylor College of Medicine, National Cancer Institute, National Institutes of Health
Find nutrients that activate immune cells
Chen’s lab focuses on understanding how metabolites, nutrients and other molecules circulating in the blood influence cancer development and response to cancer treatments. For the new study, two postdoctoral fellows, Hao Fan, PhD, and Siyuan Xia, PhD, both co-authors, assembled a “blood nutrient” compound library consisting of 255 bioactive molecules derived from nutrients. They screened the compounds in this new library for their ability to influence antitumor immunity by activating CD8+ T cells, a group of immune cells critical for killing cancerous or virus-infected cells.
After the scientists evaluated the six leading candidates in both human and mouse cells, they saw that TVA performed the best. TVA is the most abundant trans fatty acid present in human milk, but the body cannot produce it on its own. Only about 20% of TVA is broken down into other byproducts, leaving 80% circulating in the blood. “That means there must be something else it does, so we started working on it more,” Chen said.
“Seeing that a single nutrient like TVA has a very specific mechanism in a specific immune cell type…I find that really surprising and intriguing.”
— Jing Chen, Ph.D.
The researchers then carried out a series of experiments using cells and mouse models of various types of tumors. Feeding mice a TVA-enriched diet significantly reduced the tumor growth potential of melanoma and colon cancer cells compared to mice fed a control diet. The TVA diet also improved the ability of CD8+ T cells to infiltrate tumors.
The team also performed a series of molecular and genetic analyzes to understand how TVA affected T cells. These included a new technique to monitor single-stranded transcription.
Finally, the team also worked with Justin Kline, MD, professor of medicine at UChicago, to analyze blood samples taken from patients undergoing CAR-T cell immunotherapy treatment for lymphoma. They saw that patients with higher levels of TVA tended to respond better to treatment than those with lower levels. They also tested leukemia cell lines working with Wendy Stock, MD, Anjuli Seth Nayak Professor of Medicine, and saw that TVA improved the ability of an immunotherapy drug to kill leukemic cells.
Beyond Diet: Focusing on Nutritional Supplements
The study suggests that TVA could be used as a dietary supplement to aid in various T cell-based cancer treatments, although Chen notes that it is important to determine the optimized amount of the nutrient itself, not the food source. There is growing evidence about the detrimental health effects of excessive consumption of red meat and dairy, so this study should not be taken as an excuse to eat more cheeseburgers and pizza; rather, it indicates that nutritional supplements like TVA could be used to promote T cell activity. Chen believes there may be other nutrients that can do the same.
“There is early data showing that other plant fatty acids signal through a similar receptor, so we think there is a high possibility that plant nutrients could do the same by also activating the CREB pathway,” he said. .
The new research also highlights the promise of this “metabolomic” approach to understanding how building blocks of the diet affect our health. Chen said his team hopes to build a complete library of nutrients circulating in the blood to understand their impact on immunity and other biological processes such as aging.
“After millions of years of evolution, there are only a couple hundred food-derived metabolites that end up circulating in the blood, which means they might have some importance in our biology,” Chen said. “Seeing that a single nutrient like TVA has a very specific mechanism in a specific immune cell type, with a very profound physiological response at the whole organism level, I find really surprising and intriguing.”
Reference: “Trans-Vaccenic acid reprograms CD8.+ T cells and antitumor immunity” by Hao Fan, Siyuan Xia, Junhong Xiang, Yuancheng Li, Matthew O. Ross, Seon Ah Lim, Fan Yang, Jiayi Tu, Lishi Xie, Urszula Dougherty, Freya Q. Zhang, Zhong Zheng, Rukang Zhang , Rong Wu, Lei Dong, Rui Su, Xiufen Chen, Thomas Althaus, Peter A. Riedell, Patrick B. Jonker, Alexander Muir, Gregory B. Lesinski, Sarwish Rafiq, Madhav V. Dhodapkar, Wendy Stock, Olatoyosi Odenike, Anand A Patel, Joseph Opferman, Takemasa Tsuji, Junko Matsuzaki, Hardik Shah, Brandon Faubert, Shannon E. Elf, Brian Layden, B. Marc Bissonnette, Yu-Ying He, Justin Kline, Hui Mao, Kunle Odunsi, Xue Gao, Hongbo Chi , Chuan He and Jing Chen, November 22, 2023, Nature.
DOI: 10.1038/s41586-023-06749-3
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