Abstract
Brain tumors almost universally have fatal outcomes; new therapeutics are desperately needed and will only come from improved understandins of glioma biology. Exosomes are endosomally derived 30~100 nm membranous vesicles released from many cell types. Examples from GL26 cells were here purified using 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. In this study, exosomes from murine-derived GL26 cells significantly promoted in vivo tumor growth in GL26-bearing B6 mice. 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 depletion assays in vivo and LDH release assays in vitro. The treatment of mice with exosomes also led to a reduction in the percentages of CD8+T cells in splenocytes as determined by FACS analysis. Key features of CD8+T cell activity were inhibited, including release of IFN-gamma and granzyme B. There were no effects of exosomes on CD4+T cells and NK cells. Based on our data, for the first time we demonstrated that exosomes from murine derived GL26 cells promote the tumor growth by inhibition of CD8+T cells in vivo and thus may be a potential therapeutic target.
Highlights
IntroductionExosomes are small membrane vesicles found in cell culture supernatants and in different biological fluids
Exosomes from GL26 inhibit the activity of CD8+T cells in vivo
Based on the previously reports that promotion of tumor growth may due to the immunomodulation, so we subsequently study the effects of GL26 cells-derived exosomes on the immune responses via CD4+T, CD8+T and NK cells depletion in vivo
Summary
Exosomes are small membrane vesicles found in cell culture supernatants and in different biological fluids. They are 30 to 100 nm vesicles secreted by range of mammalian cells including tumor cells, reticulocytes, intestinal epithelial cells, as well as hematopoietic cells (Mallegol et al, 2005; Hendrix et al, 2011; Martin-Jaular et al, 2011). It has been reported that exosomes from murine mammary tumor cells including TS/A and 4T1 cells can inhibit NK cells cytolytic activity by down-regulation of the expression of perforin, exosomes from breast tumors inhibit the activation of T cells (Liu et al, 2006)
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