Glioblastoma (GB) is a highly aggressive primary brain cancer with poor patient prognosis. Despite aggressive multimodal standard treatment, GB remains incurable. Therapeutic resistance is driven by the extensive heterogeneity of the disease, the tumour-supportive tumour microenvironment, and the presence of GB stem cells. Notably, natural killer (NK) cells can eliminate GB stem cells. NK cell-based immunotherapy has emerged as a promising approach for GB treatment, however, the complex crosstalk between glioblastoma and NK cells remains incompletely understood.
To investigate this crosstalk in a more representative tumour-like setting, it has been first established a reproducible protocol for the generation of uniformly sized GB spheroids that recapitulate key features of GB heterogeneity and express ligands recognized by NK-cell receptors.
Building on this 3D tumour model, it has been then integrated it into the MIVO Organ-on-Chip platform to establish a more physiologically relevant model of the interaction between circulating NK cells and GB spheroids. By introducing NK cells under flow conditions, the MIVO platform enabled the study of NK–GB interactions within a dynamic microenvironment that better recapitulates the conditions experienced by immune cells in vivo.

Link to article: https://link.springer.com/article/10.1186/s12964-026-02826-y