Found a Clue to Blocking Immune Evasion of Malignant Brain Tumor Cells

Professor Lee Heung-gyu's KAIST Team Publishes Related Research Results in Nature Immunology

Mechanism of Anti-Brain Tumor Immune Response of Gamma Delta T Cells Elucidated. Provided by Korea Research Foundation.

[Asia Economy Reporter Kim Bong-su] It has been found that blocking the oxygen influx into brain tumor cells improves the immune effect of immune cells.

According to the Korea Research Foundation on the 16th, a research team led by Professor Lee Heung-kyu of the Korea Advanced Institute of Science and Technology (KAIST) published a paper on the 11th in the international journal Nature Immunology that elucidated the process of immune response reduction of gamma delta T cells caused by excessive oxygen consumption of malignant brain tumor cells.

Brain tumor cells exhibit very weak typical T cell (CD4 T, CD8 T) immune responses, which recognize and fight antigens that should remove tumors. This is because brain tumor cells do not produce many markers (MHC) that these immune cells can recognize. On the other hand, gamma delta T cells have receptors (NKG2D) that directly recognize ligands (NKG2DL (Rae1)) that frequently appear on the surface of brain tumor cells exposed to stress without antigen presentation, attracting attention as a new agent of immune response against tumors.

However, due to excessive oxygen consumption by brain tumor cells, gamma delta T cells exposed to a hypoxic environment have impaired receptor production, resulting in reduced ability to recognize brain tumor cells, which was a problem.

The research team noted that the higher the malignancy of the brain tumor, the fewer gamma delta T cells infiltrate the tumor, and the more severe the hypoxic environment. Conversely, the more gamma delta T cells infiltrated, the better the patient's prognosis. Based on this, they hypothesized that resolving the hypoxic environment and supplying appropriate oxygen to gamma delta T cells to support cell survival would normalize the immune response.

When the research team administered a compound (metformin) that blocks excessive oxygen metabolism of brain tumors together with gamma delta T cells in a brain tumor mouse model, immune cell infiltration into tumor tissue increased and survival rates improved. By resolving the hypoxic environment of gamma delta T cells, the anti-tumor immune response was enhanced.

In other words, it was demonstrated that blocking oxygen influx to brain tumor cells, which rapidly consume surrounding oxygen while proliferating vigorously, could be a clue to complement the low responsiveness of immune checkpoint inhibitors. This is evaluated as elucidating the anti-brain tumor immune response mechanism of gamma delta T cells and suggesting ways to enhance the immune response of gamma delta T cells.

Brain tumors are a type of tumor occurring in the brain and have a very poor prognosis. In particular, malignant brain tumors such as glioblastoma have an average survival period of about 1 to 2 years, are known to respond poorly to existing treatments, and tend to recur frequently.

This research was conducted with the support of the Ministry of Science and ICT and the Korea Research Foundation’s Bio-Medical Technology Development Project (Next Generation Bio Project) and the Samsung Future Technology Development Foundation.

This content was produced with the assistance of AI translation services.