TMIC-32. IMPACT OF LOW-INTENSITY TRANSCRANIAL DIRECT-CURRENT STIMULATION (TDCS) IN GLIOBLASTOMA

Abstract

Abstract The prognosis of glioblastoma (GBM) remains poor despite multiple attempts over the years to develop better treatment options for patients with this disease. Various challenges include an immunosuppressive tumor microenvironment, poor knowledge of the neuroimmune system, and the presence of the blood−brain barrier amongst others. To try and overcome some of these barriers, we used a low-intensity non-invasive transcranial direct current stimulation (tDCS) to suppress tumor growth and enhance the immune response in preclinical glioblastoma cell culture and animal model. This study reports for the first time that treatment of GBM and rGBM (recurrent GBM) cells with tDCS (50 mV/mm for 30 min), can modulate the expression of human leukocyte antigen (HLA) class II molecules such as HLA-DR alpha, HLA-DR complex, invariant chain (Ii), and HLA-DM (an important catalyst of the class II-peptide loading). Furthermore, we demonstrated in vivo that tDCS [350 μA (1 x 30 min/day) treatment 7 times (within 14 Days) showed a significant (~30%) decrease in GBM tumor growth in an orthotopic allograft GL261 GBM mouse model (at Day 41). Following tDCS treatment, our results demonstrated the downregulation of Ki-67 in treated tumors. Also, we observed the upregulation of CD38 (M1 macrophages) and CD8+ T cells in treated cells in vivo. Based on our preliminary data from in vitro and in vivo studies, we believe that this study suggests that induction of immune components of the HLA class II pathway by tDCS may be a promising therapeutic strategy for the treatment of human GBM.