title: Plasma-derived MHC class II+ exosomes from tumor-bearing mice suppress tumor antigen-specific immune responses.
abstract: Tumor-specific immunosuppression is frequently observed in tumor-bearing hosts. Exosomes are nano-sized, endosomal-derived membrane vesicles secreted by most tumor and hematopoietic cells and have been shown to actively participate in immune regulation. We previously demonstrated that antigen-specific immunosuppressive exosomes could be isolated from the blood plasma of antigen-immunized mice. Here, we demonstrate that plasma-derived exosomes isolated from mice bearing OVA-expressing tumors were able to suppress OVA-specific immune responses in a mouse delayed-type hypersensitivity model. Enrichment of tumor-derived exosomes in the plasma of mice bearing subcutaneous melanoma was not detected using an exosome-tagging approach. Instead, depletion of MHC class II(+)  vesicles from plasma-derived exosomes or using plasma-derived exosomes isolated from MHC class II-deficient mice resulted in significant abrogation of the suppressive effect. These results demonstrate that circulating host-derived, MHC class II(+)  exosomes in tumor-bearing hosts are able to suppress the immune response specific to tumor antigens.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
authors.forename: Chenjie
authors.initials: C
authors.lastname: Yang
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Ruffner
authors.forename: Seon-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Paul D
authors.initials: PD
authors.lastname: Robbins
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D055354:Exosomes / Q000276:immunology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D000949:Histocompatibility Antigens Class II; D010047:Ovalbumin