Gut
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KAIST Enhances Immunotherapy for Difficult-to-Treat Brain Tumors with Gut Microbiota
< Photo 1.(From left) Prof. Heung Kyu Lee, Department of Biological Sciences,
and Dr. Hyeon Cheol Kim>
Advanced treatments, known as immunotherapies that activate T cells—our body's immune cells—to eliminate cancer cells, have shown limited efficacy as standalone therapies for glioblastoma, the most lethal form of brain tumor. This is due to their minimal response to glioblastoma and high resistance to treatment.
Now, a KAIST research team has now demonstrated a new therapeutic strategy that can enhance the efficacy of immunotherapy for brain tumors by utilizing gut microbes and their metabolites. This also opens up possibilities for developing microbiome-based immunotherapy supplements in the future.
KAIST (President Kwang Hyung Lee) announced on July 1 that a research team led by Professor Heung Kyu Lee of the Department of Biological Sciences discovered and demonstrated a method to significantly improve the efficiency of glioblastoma immunotherapy by focusing on changes in the gut microbial ecosystem.
The research team noted that as glioblastoma progresses, the concentration of ‘tryptophan’, an important amino acid in the gut, sharply decreases, leading to changes in the gut microbial ecosystem. They discovered that by supplementing tryptophan to restore microbial diversity, specific beneficial strains activate CD8 T cells (a type of immune cell) and induce their infiltration into tumor tissues. Through a mouse model of glioblastoma, the research team confirmed that tryptophan supplementation enhanced the response of cancer-attacking T cells (especially CD8 T cells), leading to their increased migration to tumor sites such as lymph nodes and the brain.
In this process, they also revealed that ‘Duncaniella dubosii’, a beneficial commensal bacterium present in the gut, plays a crucial role. This bacterium helped T cells effectively redistribute within the body, and survival rates significantly improved when used in combination with immunotherapy (anti-PD-1).
Furthermore, it was demonstrated that even when this commensal bacterium was administered alone to germ-free mice (mice without any commensal microbes), the survival rate for glioblastoma increased. This is because the bacterium utilizes tryptophan to regulate the gut environment, and the metabolites produced in this process strengthen the ability of CD8 T cells to attack cancer cells.
Professor Heung Kyu Lee explained, "This research is a meaningful achievement, showing that even in intractable brain tumors where immune checkpoint inhibitors had no effect, a combined strategy utilizing gut microbes can significantly enhance treatment response."
Dr. Hyeon Cheol Kim of KAIST (currently a postdoctoral researcher at the Institute for Biological Sciences) participated as the first author. The research findings were published online in Cell Reports, an international journal in the life sciences, on June 26.
This research was conducted as part of the Basic Research Program and Bio & Medical Technology Development Program supported by the Ministry of Science and ICT and the National Research Foundation of Korea.
※Paper Title: Gut microbiota dysbiosis induced by brain tumor modulates the efficacy of immunotherapy
※DOI: https://doi.org/10.1016/j.celrep.2025.115825
2025.07.02 View 136 -
Regulatory T Cells Influence Liver Damage of Hepatitis A Patients
Liver damage becomes more severe with the decrease of regulatory T cells
“This research will aid the development of hepatitis A targeted drug,” said a KAIST researcher.
The KAIST Graduate School of Medical Science and Engineering’s Professor Eui-Cheol Shin and his research team have identified the mechanism, explaining how the regulatory T cells are responsible for the body’s immune system and how they have induced liver damage of hepatitis A patients.
The research results were published online in the July 9th edition of ‘Gut,’ the world’s most prominent journal in the field of gastroenterology.
Hepatitis A is an acute form of hepatitis caused by hepatitis A virus. The virus spreads through oral contact and enters the body via digestive organs.
Regulatory T cells play an important role in maintaining the homeostasis of the body’s immune system by inhibiting the activation of other immune cells. In the case of chronic viral infections, regulatory T cells are known to contribute to the duration of the infection, weakening the immune response to virus infections. However, there has been no information on what roles the regulatory T cells perform in the case of acute viral infections.
The research team used the fluorescence flow cytometry technique to determine the number and characteristics of a variety of immune cells, including regulatory T cells, in the blood of hepatitis A patients.
Consequently, the researchers confirmed that the decrease in the regulatory T cells immune inhibitory ability was consistent with a significant reduction in the number of regulatory T cells in the blood of hepatitis A patients. Furthermore, it was identified that the more noticeable decrease of regulatory T cells led to the occurrence of a more severe liver injury.
The analysis of hepatitis A patient’s blood proved that the cause of the decrease in the number and function of regulatory T cells was the increased expression of cell surface protein ‘Fas,’ which induces cell death.
Professor Shin said, “This study is the first case which proposes the mechanism for clinical aspects in not only hepatitis A, but also acute virus infection.” He added on the future prospect of the research that: “In the future, we can prevent tissue damage by inhibiting cell death of regulatory T cells for severe acute viral infections that do not have an effective treatment for the virus itself.”
[Picture]
The picture shows the process of fluorescence flow cytometry technique to study regulatory T cell in the blood of hepatitis A patients.
2014.08.11 View 11322