P08.20.B FUNCTIONAL RECOVERY OF SUPPRESSED ΓΔ T CELLS FROM GLIOBLASTOMA PATIENTS VIA SELECTIVE EXPANSION

Abstract BACKGROUND Complex interactions between glioblastoma (GBM) and the immune system shape the function of γδ T cells, particularly the Vγ9Vδ2 subset. These cells, which combine features of T and NK cells, can be rapidly expanded using zoledronic acid due to their response to mevalonate pathway dysregulation. Given their safety profile and cytotoxic potential, ex vivo expanded Vδ2 cells emerge as a promising candidate for adoptive cell therapy (ACT) in oncology. MATERIAL AND METHODS Peripheral blood from 64 glioma patients and 29 healthy donors was collected. γδ T cell subsets were analyzed by flow cytometry and compared between low grade gliomas (LGG) and GBM. Vδ2 cells from GBM patients were expanded in vitro to assess cytokine expression and cytotoxicity against U251 MG cells. Additional co-culture assays with GBM patient plasma or short-term stimulation with U251MG were performed to evaluate functional modulation. RESULTS Peripheral γδ T cells showed elevated exhaustion markers (PD-1, TIGIT, TIM-3, LAG-3) and decreased NKG2D and CD226 expression in the LGG and GBM group when compared to healthy donors. Despite this, Vδ2 cells from GBM patients expanded efficiently in vitro, secreted high levels of IL-1β, IFN-γ, TNF, and IL-17A, and exhibited potent cytotoxicity against U251 MG cells. Functional recovery was confirmed by increased CD107a expression and GBM cell killing in co-culture. Plasma from GBM patients impaired activation but did not abolish cytotoxic capacity post-expansion, supporting the feasibility of ACT using patient-derived Vδ2 cells. CONCLUSION Despite profound peripheral immunosuppression in glioma patients, Vγ9Vδ2 T cells can recover cytotoxic function cells upon in vitro expansion, supporting their potential use in adoptive cell therapy against GBM.