title: Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model.
abstract: Exosomes are endosome-derived small membrane vesicles that are secreted by most cell types including tumor cells. Tumor-derived exosomes usually contain tumor antigens and have been used as a source of tumor antigens to stimulate anti-tumor immune responses. However, many reports also suggest that tumor-derived exosomes can facilitate tumor immune evasion through different mechanisms, most of which are antigen-independent. In the present study we used a mouse model of delayed-type hypersensitivity (DTH) and demonstrated that local administration of tumor-derived exosomes carrying the model antigen chicken ovalbumin (OVA) resulted in the suppression of DTH response in an antigen-specific manner. Analysis of exosome trafficking demonstrated that following local injection, tumor-derived exosomes were internalized by CD11c+ cells and transported to the draining LN. Exosome-mediated DTH suppression is associated with increased mRNA levels of TGF-β1 and IL-4 in the draining LN. The tumor-derived exosomes examined were also found to inhibit DC maturation. Taken together, our results suggest a role for tumor-derived exosomes in inducing tumor antigen-specific immunosuppression, possibly by modulating the function of APCs.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Chenjie
authors.initials: C
authors.lastname: Yang
authors.forename: Seon-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Bianco
authors.forename: Paul D
authors.initials: PD
authors.lastname: Robbins
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D055354:Exosomes / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics; D051379:Mice; D010047:Ovalbumin / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4; D010047:Ovalbumin