A study from Weill Cornell Medicine reveals that gut bacteria play a crucial role in determining whether the amino acid asparagine promotes tumor growth or activates immune cells against cancer. Published in the journal Cell Microbe and Host on January 2, the research may lead to innovative cancer treatment methods that reshape the gut microbiome or dietary approaches to deprive tumors while enhancing immune functionality.
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Dr. Chunjun (CJ) Guo, an associate professor of immunology at Weill Cornell, emphasized the need to consider how diet, gut bacteria, and immune cells interact in cancer dynamics. The research was conducted in collaboration with Dr. David Artis and Dr. Nicholas Collins, also from Weill Cornell.
Initial experiments demonstrated that certain bacteria could deplete specific amino acids and influence tumor progression. The focus shifted to asparagine, which is essential for protein synthesis and cell survival. In tumor environments lacking nutrients, both cancer cells and CD8+ T cells rely on asparagine for their functions.
The researchers examined Bacteroides ovatus, a common gut bacterium, which has a gene called bo-ansB that breaks down asparagine. In mouse models, it was found that when the bo-ansB gene was active, the bacteria consumed more asparagine, leading to lower levels entering the bloodstream and reaching tumors. Conversely, when the gene was knocked out, asparagine levels in circulation increased, benefiting tumor growth.
Results indicated that in colorectal cancer models fed high asparagine diets, the presence of B. ovatus with the bo-ansB gene facilitated tumor growth. If the bacteria lacked this gene, the high asparagine diet instead prompted CD8+ T cells to enter a beneficial “stem-like” state, enhancing their ability to combat tumors.
Elevated asparagine levels led CD8+ T cells to express more of the transporter protein SLC1A5, vital for fighting cancer. Stem-like CD8+ T cells can generate renewably into cancer-fighting T cells. Blocking SLC1A5 nullified the positive effects of increased asparagine levels on immune activity.
Moving forward, Dr. Guo's lab aims to investigate additional pathways that might influence tumor burden by either hindering growth or bolstering antitumor activity. The potential for microbiota-produced enzymes and metabolites to serve as cancer biomarkers is also being explored. Dr. Collins highlighted the importance of personalized therapies, suggesting tailored diets aligned with individual microbiomes could enhance the immune response against cancer.
This study was supported by various grants from the National Institutes of Health and funding from the Kenneth Rainin Foundation and the Crohn's & Colitis Foundation.