New possibilities for treating intractable brain tumors unveiled

Immunotherapy, which enhances the immune system’s T cell response to eliminate cancer cells, has emerged as a key approach in cancer treatment. However, in the case of glioblastoma, an aggressive and treatment-resistant brain tumor, numerous clinical trials have failed to confirm its efficacy.

Korean researchers have analyzed the mechanisms that cause T cells to lose function or weaken after prolonged exposure to antigens in such intractable cancers, identifying key control factors in T cell activation and clarifying the mechanisms that enhance therapeutic effectiveness.

Professor Heung Kyu Lee’s team from KAIST’s Department of Biological Sciences, in collaboration with the Korea Research Institute of Chemical Technology, has confirmed improved survival rates in a glioblastoma mouse model.

The study was published online on October 26 in the Journal for ImmunoTherapy of Cancer.

By removing the inhibitory Fc gamma receptor (FcγRIIB), the research team was able to restore the responsiveness of cytotoxic T cells to immune checkpoint inhibitors, leading to enhanced anticancer activity.

The research team examined the effect of FcγRIIB, an inhibitory receptor recently found in cytotoxic T cells, on tumor-infiltrating T cells and the therapeutic effectiveness of the anti-PD-1 immune checkpoint inhibitor.

Their findings showed that deleting FcγRIIB induced the increase of tumor antigen-specific memory T cells, which helps to suppress exhaustion, enhances stem-like qualities, and reactivates T cell-mediated antitumor immunity, particularly in response to anti-PD-1 treatment. Furthermore, FcγRIIB deletion led to an increase in antigen-specific memory T cells that maintained continuous infiltration into the tumor tissue.

This study presents a new therapeutic target for tumors unresponsive to immune checkpoint inhibitors and demonstrates that combining FcγRIIB inhibition with anti-PD-1 treatment can produce synergistic effects, potentially improving therapeutic outcomes for tumors like glioblastoma, which typically show resistance to anti-PD-1 therapy.

Professor Heung Kyu Lee explained, “This study offers a way to overcome clinical failures in treating brain tumors with immune checkpoint therapy and opens possibilities for broader applications to other intractable cancers. It also highlights the potential of utilizing cytotoxic T cells for tumor cell therapy.”