A recent study from The University of Texas MD Anderson Cancer Center has identified BATF2 as a tumor suppressor that can be silenced by glutamine in the tumor microenvironment, leading to a reduced immune response in head and neck cancer models. The research, published in Nature Communications, was led by Yu Leo Lei, D.D.S., Ph.D., associate professor of Head and Neck Surgery, Cancer Biology and Translational Molecular Pathology.
According to Lei, "The canonical tumor suppressors are frequently mutated or lost at the genetic level. Emerging evidence highlights the importance of a new type of tumor suppressor that is not frequently mutated but is epigenetically inhibited by unique metabolic cues in the tumor microenvironment. This study characterizes a novel oral cancer tumor suppressor that drives immune surveillance but is inhibited by high levels of glutamine."
BATF2 plays a role in regulating immune responses and maintaining anti-tumor surveillance. It is expressed by epithelial and myeloid cells and can activate the STING pathway, which is important for innate immunity through Type-I interferon (IFN-I) production. The researchers found that higher BATF2 levels in patient tumors were associated with stronger IFN-I and Th1 immune signatures, indicating better recruitment of immune cells to attack tumors.
The study also found an inverse relationship between BATF2/IFN-I genes and genes involved in glutamine metabolism. A diet rich in glutamine was shown to silence BATF2 expression, weaken the immune response, reduce IFN-I production, and increase oxygen consumption—conditions that allow cancer cells to grow unchecked. However, drugs targeting glutamine metabolism were able to restore IFN-I production and make cancer cells more responsive to treatments aimed at the STING pathway.
These findings suggest that managing glutamine levels could enhance BATF2 expression and potentially improve immune responses for patients with head and neck cancers resistant to current therapies targeting the STING pathway. Further studies will be needed before these results can be applied clinically.
