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Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model

Academic Article
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Overview

authors

  • Yang, C. J.
  • Kim, S. H.
  • Bianco, N. R.
  • Robbins, Paul D.

publication date

  • 2011

journal

  • PLoS One  Journal

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.

subject areas

  • Animals
  • Antigen-Presenting Cells
  • Antigens, Neoplasm
  • Exosomes
  • Hypersensitivity, Delayed
  • Interleukin-4
  • Mice
  • Ovalbumin
  • RNA, Messenger
  • Transforming Growth Factor beta1
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Identity

PubMed Central ID

  • PMC3149056

International Standard Serial Number (ISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0022517

PubMed ID

  • 21829629
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Additional Document Info

start page

  • e22517

volume

  • 6

issue

  • 8

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