In glioblastoma treatment, immune-cell order makes the difference, Korean researchers find

A Korean research team has become the first in the world to establish that the sequence of interactions between immune cells and cancer cells is a key factor determining treatment efficacy in glioblastoma, a type of brain tumor.

A joint research team led by Sungkyunkwan University Professor Park Seong-su and Seoul National University College of Medicine Professor Baek Seon-ha announced on the 3rd that it had published these findings in Neuro-Oncology, an international journal specializing in brain tumors.

Glioblastoma is considered one of the most lethal brain tumors. It is characterized by extensive infiltration of microglia, the brain’s immune cells, into the tumor, creating a potent immunosuppressive environment. As a result, natural killer (NK) cells, which directly attack cancer cells, have difficulty infiltrating the tumor, limiting treatment efficacy.

To analyze these time-dependent interactions, the research team developed a multichannel microfluidic platform. The platform can precisely control the order and timing of cell injection into a 3-dimensional tumor model.

The results showed that when microglia reached the cancer cells first, STAT3 signaling was activated, blocking NK-cell infiltration and promoting tumor growth. In contrast, when NK cells arrived first, the immune-activating factor IL12A was strongly expressed in the cancer cells, producing a sustained tumor-suppressive effect. Even with the same cellular composition, the tumor immune response differed dramatically depending on the sequence of immune-cell activity.

The research team also demonstrated the technology’s potential for clinical application using patient-derived glioblastoma cells. Combined administration of the STAT3 inhibitor WP1066 and temozolomide (TMZ) substantially increased NK-cell infiltration into the tumor and produced a synergistic improvement in tumor-cell killing.

The core technology has been commercialized by Organoplus under the name CANORGAN and is available for research use.

“We used engineering technology to elucidate the time-dependent interactions among immune cells within tumor tissue, which are difficult to observe with animal models or conventional culture methods,” Professor Park Seong-su said. “We will continue developing the technology as a patient-specific drug-screening platform for various treatment-resistant solid tumors.”

The study was supported by the Ministry of Science and ICT and the National Research Foundation of Korea (NRF).