A study conducted at the University of Chicago reveals that trans-vaccenic acid (TVA) in meat and dairy products increases the effectiveness of CD8 + T cells in fighting cancer. Higher levels of TVA are associated with better immunotherapy responses, highlighting its potential as a complementary cancer treatment.
scientists Trans-vaccenic acid (TVA), a long-chain fatty acid found in meat and dairy products from grazing animals such as cows and sheep, improves the ability of CD8+ T cells to infiltrate tumors and kill cancer cells, according to a new study. Researchers from the University of Chicago.
The research was published in the journal Nov. 22 NatureIt also shows that patients with higher levels of circulating TVA respond better to immunotherapy; this suggests that it may have potential as a nutritional supplement complementary to clinical treatments for cancer.
“There are many studies trying to unravel the link between diet and human health, and understanding the underlying mechanisms is very difficult due to the wide variety of foods people eat. But if we focus solely on the nutrients and metabolites derived from food, we begin to see how they influence physiology and pathology,” said Jing Chen, the Janet Davison Rowley Distinguished Service Professor of Medicine at UChicago and one of the senior authors of the new study. “By focusing on nutrients that can activate T-cell responses “We found a nutrient that actually boosts anti-tumor immunity by activating an important immune pathway.”
The research of Jing Chen, Chuan He, and their team suggests that TVA may have the potential to be a nutritional supplement to complement clinical treatments for cancer. Contributors: Rita Elena Serda, Baylor College of Medicine Duncan Comprehensive Cancer Center, National Cancer Institute, National Institutes of Health
Finding Nutrients That Activate Immune Cells
Chen’s lab focuses on understanding how metabolites, nutrients, and other molecules circulating in the blood affect the development of cancer and the response to cancer treatments. For the new study, two postdoctoral researchers, Hao Fan and Siyuan Xia, PhD, both co-authors, created a “blood nutrient” compound library of 255 bioactive molecules derived from nutrients. They screened the compounds in this new library for their ability to affect anti-tumor immunity by activating CD8+ T cells, a group of immune cells critical for killing cancerous or virally infected cells.
After evaluating the top six candidates in both human and mouse cells, the scientists found that TVA performed best. TVA is the most abundant trans fatty acid in human milk, but the body cannot produce it on its own. Only 20% of TVA is broken down into other byproducts and 80% remains circulating in the blood. “That meant there had to be something else he was doing, so we started working on it more,” Chen said.
“To see that a single nutrient like TVA has a very targeted mechanism on the targeted immune cell type… I find that really surprising and intriguing.”
— Jing Chen, PhD
The researchers then conducted a series of experiments with cells of various tumor types and mouse models. 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 increased the ability of CD8+ T cells to infiltrate tumors.
The team also performed a series of molecular and genetic analyzes to understand how TVA affects T cells. These included a new technique for monitoring single-strand transcription.
Finally, the team also worked with UChicago Professor of Medicine Justin Kline, MD, to analyze blood samples from patients receiving CAR-T cell immunotherapy treatment for lymphoma. They found that patients with higher TVA levels tended to respond better to treatment than those with lower levels. They also worked with Anjuli Seth Nayak Professor of Medicine Wendy Stock, MD, to test cell lines from leukemia and found that TVA increased the ability of an immunotherapy drug to kill leukemia cells.
Beyond Diet: Focusing on Supplements
The study suggests that TVA could be used as a nutritional supplement to assist with various T-cell-based cancer treatments; However, Chen points out that it is important to determine the optimized amount of the nutrient itself, not the nutrient source. There is growing evidence of the harmful health effects of consuming too much red meat and dairy; Therefore, this study should not be taken as an excuse to eat more cheeseburgers and pizza; rather, it indicates that nutritional supplements such as TVA can be used to support T cell activity. Chen thinks there may be other foods that can do the same thing.
“There is early data showing that other fatty acids from plants also signal through a similar receptor, so we believe it is likely that nutrients from plants may do the same by activating the CREB pathway,” he said.
The new research also highlights the promise of this “metabolomics” approach to understanding how the building blocks of diet affect our health. Chen said his team hopes to create a comprehensive library of blood-circulating nutrients to understand their effects on immunity and other biological processes such as aging.
“After millions of years of evolution, there are only a few hundred metabolites derived from food and circulating in the blood, which means they may have some importance in our biology,” Chen said. “To see that a single nutrient like TVA has a very targeted mechanism on a targeted immune cell type and has such a profound physiological response at the whole organism level, I find that really surprising and intriguing.”
Reference: “TranceVaxenic acid reprograms CD8+ T cells and anti-tumor 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, 22 November 2023, Nature.
DOI: 10.1038/s41586-023-06749-3
The study was supported by the following organizations: (function(d,s,id){var js,fjs=d.getElementsByTagName(s)[0];if(d.getElementById(id))return;js=d.createElement(s);js.id=id;js.src="https://connect.facebook.net/en_US/sdk.js#xfbml=1&version=v2.6";fjs.parentNode.insertBefore(js,fjs);}(document,'script','facebook-jssdk'));