title: Exosomes from murine-derived GL26 cells promote glioblastoma tumor growth by reducing number and function of CD8+T cells.
abstract: OBJECTIVE
  Brain tumors almost universally have fatal outcomes; new therapeutics are desperately needed and will only come from improved understandins of glioma biology.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Liu
authors.forename: Yu-Bin
authors.initials: YB
authors.lastname: Wang
authors.forename: Xian-Hou
authors.initials: XH
authors.lastname: Yuan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D055354:Exosomes; D005260:Female; D005909:Glioblastoma / Q000276:immunology* / Q000473:pathology*; D053804:Granzymes / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural; D007770:L-Lactate Dehydrogenase / Q000097:blood; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology
chemical_list: D007371:Interferon-gamma; D007770:L-Lactate Dehydrogenase; D053804:Granzymes