Potential new cure found for treating glioblastoma resistant to immunotherapy

Korean researchers have found a way to increase the efficacy of immunotherapy against glioblastoma, an incurable brain tumor.

The discovery is good news because immune checkpoint inhibitors, which boost the anticancer immunity of T cells that kill cancer cells, are ineffective in treating glioblastoma.

The Korea Advanced Institute of Science and Technology (KAIST) said Wednesday that a research team led by Professor Lee Heung-kyu of the Department of Life Sciences discovered a new possibility for glioblastoma treatment in collaboration with the Korea Research Institute of Chemical Technology (KRICT)’s Center for Infectious Disease Prevention and Diagnosis Technology.

The team found that inhibitory Fc gamma receptor (FcγRIIB) deletion restored cytotoxic T-cell refractoriness to immune checkpoint inhibitors in a glioblastoma model in mice, inducing enhanced anticancer activity and improving survival.

Results showed that the deletion of FcγRIIB, which is found on cytotoxic T cells, increased tumor antigen-specific memory T cells. These T-cell subtypes inhibited de-evolution and enhanced stem cell properties, leading to a restored T-cell anticancer immune response to anti-PD-1 treatment.

The team also found that FcγRIIB deletion resulted in a relatively significant increase in antigen-specific memory T cells and led to T-cell infiltration into tumor tissue.

“This study provides a novel therapeutic target for tumors refractory to immune checkpoint inhibitors,” Professor Lee said. “Combining FcγRIIB inhibition with anti-PD-1 therapy may have a synergistic effect in tumors refractory to anti-PD-1 therapy, such as glioblastoma.”

Professor Lee said the results suggest the possibility of overcoming the clinical failure of brain tumor treatment with immune checkpoint inhibitors and the possibility of universal application to other refractory tumors. The results also confirm the potential for future use and access to cytotoxic T cells for tumor cell therapy.

The research paper, “Inhibitory Fcγ receptor deletion enhances CD8 T cell stemness increasing anti-PD-1 therapy responsiveness against glioblastoma,” in which Dr. Ku Keun-bon of KAIST, who is also a senior researcher at the KRICT’s research center, was published on Oct. 26 in the online edition of the Journal for ImmunoTherapy of Cancer, an international journal published by the Society for Immunotherapy of Cancer.