A study from the University of Chicago reveals that trans-vaccenic acid (TVA) in meat and dairy items increases the effectiveness of CD8+ T cells in combating cancer. Higher TVA levels correlate with better immunotherapy reactions, highlighting its prospective as an additional cancer treatment.
Scientists at the University of Chicago found that trans-vaccenic acid (TVA), a fatty acid found in dairy, lamb, and beef items, enhances the ability of immune cells to combat growths.
Trans-vaccenic acid (TVA), a long-chain fat found in meat and dairy items from grazing animals such as cows and sheep, improves the ability of CD8+ T cells to eliminate and infiltrate growths cancer cells, according to a new research study by scientists from the University of Chicago.
The research study, published on November 22 in the journal Nature, also shows that patients with greater levels of TVA distributing in the blood responded better to immunotherapy, suggesting that it could have possible as a nutritional supplement to complement clinical treatments for cancer.
They screened the compounds in this brand-new library for their capability to affect anti-tumor resistance by triggering CD8+ T cells, a group of immune cells important for killing malignant or virally infected cells.
Feeding mice a diet plan improved with TVA substantially decreased the tumor development capacity of melanoma and colon cancer cells compared to mice fed a control diet. These extra assays, done by both the Chen and He labs, revealed that TVA inactivates a receptor on the cell surface called GPR43 which is normally activated by short-chain fatty acids frequently produced by gut microbiota. They likewise evaluated cell lines from leukemia by working with Wendy Stock, MD, the Anjuli Seth Nayak Professor of Medicine, and saw that TVA enhanced the ability of an immunotherapy drug to eliminate leukemia cells.
There is a growing body of evidence about the damaging health effects of consuming too much red meat and dairy, so this study shouldnt be taken as an excuse to eat more cheeseburgers and pizza; rather, it suggests that nutrient supplements such as TVA could be utilized to promote T cell activity.
” There are many research studies attempting to understand the link in between diet plan and human health, and its really challenging to comprehend the underlying mechanisms because of the wide array of foods individuals consume. If we focus on just the nutrients and metabolites obtained from food, we start to see how they influence physiology and pathology,” stated Jing Chen, PhD, the Janet Davison Rowley Distinguished Service Professor of Medicine at UChicago and one of the senior authors of the new study. “By concentrating on nutrients that can activate T cell responses, we discovered one that actually boosts anti-tumor resistance by activating an essential immune pathway.”
Research by Jing Chen, Chuan He, and team recommends that TVA might have possible as a nutritional supplement to complement medical treatments for cancer. Credit: Rita Elena Serda, Duncan Comprehensive Cancer Center at Baylor College of Medicine, National Cancer Institute, National Institutes of Health
Finding Nutrients That Activate Immune Cells
Chens lab focuses on comprehending how metabolites, nutrients, and other molecules distributing in the blood affect the development of cancer and action to cancer treatments. For the brand-new study, two postdoctoral fellows, Hao Fan, PhD and Siyuan Xia, PhD, both co-first authors, put together a “blood nutrient” compound library consisting of 255 bioactive molecules originated from nutrients. They evaluated the substances in this new library for their ability to influence anti-tumor immunity by activating CD8+ T cells, a group of immune cells important for eliminating malignant or virally infected cells.
After the researchers examined the top six prospects in both human and mouse cells, they saw that TVA carried out the finest. TVA is the most plentiful trans fatty acid present in human milk, but the body can not produce it on its own.
” To see that a single nutrient like TVA has actually a really targeted system on a targeted immune cell type … I find that really fantastic and interesting.”
— Jing Chen, PhD
The scientists then carried out a series of explores cells and mouse models of varied growth types. Feeding mice a diet plan enhanced with TVA substantially reduced the tumor growth capacity of melanoma and colon cancer cells compared to mice fed a control diet plan. The TVA diet also boosted the capability of CD8+ T cells to infiltrate growths.
The team likewise performed a series of hereditary and molecular analyses to understand how TVA was affecting the T cells. These consisted of a brand-new strategy for monitoring transcription of single-stranded DNA called kethoxal-assisted single-stranded DNA sequencing, or KAS-seq, developed by Chuan He, PhD, the John T. Wilson Distinguished Service Professor of Chemistry at UChicago and another senior author of the study. These additional assays, done by both the Chen and He labs, revealed that TVA suspends a receptor on the cell surface called GPR43 which is usually activated by short-chain fats typically produced by gut microbiota. TVA subdues these short-chain fatty acids and triggers a cellular signaling procedure referred to as the CREB path, which is included in a variety of functions consisting of cellular growth, survival, and differentiation. The team also revealed that mouse models where the GPR43 receptor was solely gotten rid of from CD8+ T cells likewise lacked their enhanced tumor-fighting ability.
The team also worked with Justin Kline, MD, Professor of Medicine at UChicago, to evaluate blood samples taken from patients undergoing CAR-T cell immunotherapy treatment for lymphoma. They saw that patients with greater levels of TVA tended to respond to treatment much better than those with lower levels. They likewise evaluated cell lines from leukemia by dealing with Wendy Stock, MD, the Anjuli Seth Nayak Professor of Medicine, and saw that TVA improved the ability of an immunotherapy drug to kill leukemia cells.
Beyond Diet: Focusing on Nutrient Supplements
The research study recommends that TVA might be used as a dietary supplement to help different T cell-based cancer treatments, although Chen explains that it is essential to determine the optimized quantity of the nutrient itself, not the food source. There is a growing body of evidence about the harmful health results of taking in excessive red meat and dairy, so this study should not be taken as an excuse to consume more cheeseburgers and pizza; rather, it suggests that nutrient supplements such as TVA could be utilized to promote T cell activity. Chen thinks there might be other nutrients that can do the same.
” There is early data showing that other fatty acids from plants signal through a comparable receptor, so our company believe there is a high possibility that nutrients from plants can do the exact same thing by activating the CREB pathway too,” he said.
The new research also highlights the promise of this “metabolomic” method to understanding how the structure blocks of diet plan impact our health. Chen said his team wishes to develop a detailed library of nutrients distributing in the blood to understand their effect on resistance and other biological processes like aging.
” After millions of years of development, there are only a couple hundred metabolites originated from food that end up distributing in the blood, so that suggests they might have some importance in our biology,” Chen said. “To see that a single nutrient like TVA has a really targeted system on a targeted immune cell type, with a really extensive physiological reaction at the entire organism level– I discover that appealing and truly remarkable.”
Reference: “Trans-vaccenic acid reprograms CD8+ T cells and anti-tumour 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 National Institutes of Health (grants CA140515, CA174786, CA276568, 1375 HG006827, K99ES034084), a UChicago Biological Sciences Division Pilot Project Award, the Ludwig Center at UChicago, the Sigal Fellowship in Immuno-oncology, the Margaret E. Early Medical Research Trust, the AASLD Foundation a Harborview Foundation Gift Fund, and the Howard Hughes Medical Institute.