TMOD-07DIFFERENCES IN TUMOR GRAFT ACCEPTANCE OF 261 GLIOBLASTOMA MULTITFORME (GBM) CELL LINE BETWEEN WILD TYPE C57BL6, CD74 DEFICIENT, AND GAMMA DELTA TCR DEFICIENT MICE

Abstract

BACKGROUND AND SIGNIFICANCE: Glioblastoma Multiforme (GBM) is a deadly and highly aggressive brain tumor with grim prognosis. At present none of the treatment strategies extend the life of most patients beyond a year. A contribution from the immune system in the control and/or growth of tumors is currently under intense investigation. However, the strategies GBM cells use to hide from the immune system are poorly understood. EXPERIMENTAL APPROACH: To address this issue, we compared the tumor graft acceptance of the mouse GBM 261 neurosphere (mouse glioma cell line/derived from a tumor from a C57Bl6 strain background) into C57Bl6 mice with three genetic modifications (CD74, invariant chain deficient mice; gamma delta knockout mice; and control, wild type C57Bl6 mice). Neurospheres were made from 261 cells by plating 10^5 cells/mL in DMEM/F12 media supplemented with 20 ng/mL EGF and 10 ng/mL bFGF, 0.002% heparin and B27 supplement without retinol. Cells started showing neurosphere morphology at around 6 days. The 261 neurospheres were injected stereotactically in the caudate nucleus and mice were observed for 4-6 weeks after neurosphere injection. RESULTS: The data showed that the tumor acceptance in C57Bl6 mice was higher than acceptance in either CD74 deficient or Gamma Delta TCR deficient mice. In addition, C57Bl6 mice showed rapid tumor growth with robust neurological deficit as early as 4 weeks. No neurological deficit was observed in invariant chain deficient mice or gamma delta knockout mice. CONCLUSIONS: These data suggest a contribution from CD74 as well as gamma delta T cells in tumor graft acceptance. Further experiments are ongoing to determine the potential role of CD74 and/or gamma delta T cells in the progression of GBM.