J Neurooncol. 2025 Jul 21. doi: 10.1007/s11060-025-05150-6. Online ahead of print.ABSTRACTPURPOSE: Glioblastoma is a highly aggressive and invasive brain tumor that can interact dynamically with its surrounding tumor microenvironment, including resident and infiltrating-immune cells. These interactions largely govern glioblastoma progression and resistance to therapy. Glioblastoma cells can actively modulate immune cell functions, either by inhibiting immune responses or reprogramming immune cells. This study explores the dynamic interaction between glioblastoma cells and T cells.METHODS: The connections between glioblastoma cells and T cells were analyzed by immunohistochemistry, immunofluorescence and scanning electron microscopy. Inhibition of tunneling nanotubes (TNTs) between glioblastoma cells and T cells was performed using carbenoxolone. Fluorogenic probes were used for mitochondrial membrane potential and reactive oxygen species (ROS) in mitochondria, glioblastoma cells and T cells after co-culture. Viability and LAG-3 levels were analyzed in T cells.RESULTS: Glioblastoma cells show connections between themselves and forms physical connections with T cells through TNTs. Glioblastoma cells hijack mitochondria from T cells through these connections and effect was reversed on using carbenoxolone. Glioblastoma cells show increased mitochondrial membrane potential and decreased mitochondrial ROS after co-culture, while ROS was increased in glioblastoma cells and decreased in T cells.CONCLUSION: We show for the first time that glioblastoma cells and T cells physically connect through TNTs. Most importantly, glioblastoma cells hijack the mitochondria of T cells for its own advantage. By focusing on these complex tumor-immune cell interactions, this study aims to uncover a novel mode of physical communication in glioblastoma microenvironment.PMID:40690183 | DOI:10.1007/s11060-025-05150-6