Enhancing Brain Tumor Immunotherapy Through Gut Microbes and Tryptophan Supplementation

Recent advancements in cancer treatment have focused on immunotherapy, which activates the body's immune cells, especially T cells, to target and destroy tumor cells. However, traditional immunotherapies have shown limited success against glioblastoma, one of the most aggressive and treatment-resistant brain tumors, due to the tumor's high resistance and minimal responsiveness.

In a groundbreaking study published in Cell Reports, researchers from the Korea Advanced Institute of Science and Technology (KAIST) have pioneered a new approach to improve immunotherapy outcomes for brain tumors by leveraging the gut microbiome and its metabolites. Led by Professor Heung Kyu Lee, the team discovered that manipulating the gut microbial ecosystem can significantly enhance immune responses against glioblastoma.

The study highlights that as glioblastoma progresses, there is a marked decrease in tryptophan, an essential amino acid found in the gut, which leads to disruptions in microbial diversity. Restoring tryptophan levels through supplementation was found to promote beneficial gut bacteria, such as Duncaniella dubosii, which plays a crucial role in activating CD8 T cells. These T cells are vital for attacking tumor cells, and their infiltration into brain tumors and lymph nodes was markedly increased with tryptophan supplementation.

Furthermore, the researchers demonstrated that administering Duncaniella dubosii alone to germ-free mice—those without any existing microbiota—resulted in improved survival rates, attributed to enhanced T cell activity. When combined with immune checkpoint inhibitors like anti-PD-1 therapy, the presence of this bacterium led to a notable increase in tumor regression and survival.

Professor Lee emphasized, "This research provides promising evidence that even for intractable brain tumors where conventional immune therapies fail, integrating gut microbiota modulation can boost treatment effectiveness."

This discovery opens new avenues for microbiome-based adjunct therapies for brain cancer, emphasizing personalized approaches that include microbial and metabolic interventions alongside existing treatments. The findings suggest that dietary strategies or probiotic supplements targeting tryptophan levels and specific gut bacteria could become an important part of future brain tumor management.

For more details, the full research can be accessed in *Cell Reports" and is a significant step toward integrating microbiome science into neuro-oncology treatments.