research
< 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.
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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
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