title: The limited capacity of malignant glioma-derived exosomes to suppress peripheral immune effectors.
abstract: Tumor-derived microvesicular exosomes permit intercellular communication both locally and systemically by delivering a snapshot of the tumor cell's constituents. We thus investigated whether exosomes mediate malignant glioma's facility for inducing peripheral immunosuppression. In Western blot and RT-PCR analyses, glioma-derived exosomes displayed exosome-specific markers, but failed to recapitulate the antigen-presentation machinery, surface co-modulatory signals, or immunosuppressive mediator status of their parent tumor cells. Treatment with glioma-derived exosomes promoted immunosuppressive HLA-DR(low) monocytic phenotypes, but failed to induce monocytic PD-L1 expression or alter the activation of cytotoxic T-cells from patients' peripheral blood by FACS and RT-PCR analyses. Our results suggest that malignant glioma-derived exosomes are restricted in their capacity to directly prime peripheral immunosuppression.
authors.affiliation: Department of Neurological Surgery, UCSF, San Francisco, CA, USA; Clinical and Translational Science Institute, UCSF, San Francisco, CA, USA.
authors.forename: J Bryan
authors.initials: JB
authors.lastname: Iorgulescu
authors.affiliation: Department of Neurological Surgery, UCSF, San Francisco, CA, USA. Electronic address: Michael.ivan@jhsmiami.org.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Ivan
authors.affiliation: Department of Neurological Surgery, UCSF, San Francisco, CA, USA; Clinical and Translational Science Institute, UCSF, San Francisco, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Safaee
authors.affiliation: Department of Neurological Surgery, UCSF, San Francisco, CA, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Parsa
mesh_terms: D001253:Astrocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D055354:Exosomes / Q000276:immunology*; D005910:Glioma / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D009000:Monocytes / Q000276:immunology
keywords: Exosome; Glioma; Immunosuppression; Immunotherapy; Microvesicle