Exosomes from Murine-derived GL26 Cells Promote Glioblastoma Tumor Growth by Reducing Number and Function of CD8+T Cells

Aim: Brain tumors almost universally have fatal outcomes; new therapeutics are desperately needed andwill only come from improved understandins of glioma biology.
Methods: Exosomes are endosomally derived30~100 nm membranous vesicles released from many cell types. Examples from GL26 cells were here purifiedusing density gradient ultracentrifugation and monitored for effects on GL26 tumor growth in C57BL/6j mice(H-2b). Lactate dehydrogenase release assays were used to detect the cytotoxic activity of CD8+T and NK cells.Percentages of immune cells producing intracellular cytokines were analyzed by FACS.
Results: In this study,exosomes from murine-derived GL26 cells significantly promoted in vivo tumor growth in GL26-bearing B6mice. Then we further analyzed the effects of the GL26 cells-derived exosomes on immune cells including CD8+T,CD4+T and NK cells. Inhibition of CD8+T cell cytotoxic activity was demonstrated by CD8+T cell depletionassays in vivo and LDH release assays in vitro. The treatment of mice with exosomes also led to a reduction inthe percentages of CD8+T cells in splenocytes as determined by FACS analysis. Key features of CD8+T cellactivity were inhibited, including release of IFN-gamma and granzyme B. There were no effects of exosomeson CD4+T cells and NK cells.
Conclusion: Based on our data, for the first time we demonstrated that exosomesfrom murine derived GL26 cells promote the tumor growth by inhibition of CD8+T cells in vivo and thus maybe a potential therapeutic target.