IMMU-30. Trogocytosis-Mediated Acquisition of TIM-3 by Glioblastoma Cells Enhances Tumor Malignancy

Abstract Trogocytosis is a contact-dependent cellular phenomenon involving direct transfer of membrane fragments and surface molecules between interacting cells, influencing various biological processes including intercellular communication, immune regulation, and responses to pathogens. While its roles are increasingly recognized, occurrences in brain tumors remain poorly defined. Here, we report a novel mechanism in which human glioblastoma (GBM) cells acquire the immune checkpoint receptor TIM-3 from macrophages via trogocytosis, leading to increased tumor malignancy. Our study demonstrates that this transfer of TIM-3 from macrophages to GBM cells occurs rapidly through direct cell-to-cell attachment. Importantly, this acquisition did not alter the intrinsic TIM-3 transcript expression within GBM cells, and the acquired TIM-3 protein was maintained for several hours on the cell surface. Functionally, TIM-3 acquired via trogocytosis actively induced key malignant behaviors in GBM cells, including enhanced proliferation, migration, and invasion. Furthermore, inhibiting actin polymerization, a known mechanism underlying trogocytosis, significantly reduced the acquisition of TIM-3 by GBM cells. Mechanistically, GBM cells that acquired TIM-3 through trogocytosis exhibited activation of the pro-tumorigenic IL-6-pSTAT3 Tyr705 signaling pathway. Collectively, our findings highlight the occurrence of trogocytosis in central nervous system (CNS) tumors and reveal a pathological modulation of glioblastoma malignant properties by acquired TIM-3. This study identifies a novel mechanism of intercellular communication that contributes to GBM progression, potentially offering new therapeutic avenues.