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

Yang, C and Kim, SH and Bianco, NR and Robbins, PD (2011) Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model. PLoS ONE, 6 (8).

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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. © 2011 Yang et al.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Yang, C
Kim, SH
Bianco, NR
Robbins, PDprobb@pitt.eduPROBB
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorKanellopoulos, JeanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 5 August 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 8
DOI or Unique Handle: 10.1371/journal.pone.0022517
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
Refereed: Yes
MeSH Headings: Animals; Antigen-Presenting Cells--immunology; Antigens, Neoplasm--immunology; Exosomes--immunology; Hypersensitivity, Delayed--immunology; Interleukin-4--genetics; Mice; Ovalbumin--administration & dosage; RNA, Messenger--genetics; Transforming Growth Factor beta1--biosynthesis; Transforming Growth Factor beta1--genetics
Other ID: NLM PMC3149056
PubMed Central ID: PMC3149056
PubMed ID: 21829629
Date Deposited: 05 Sep 2012 18:14
Last Modified: 13 Oct 2017 22:57
URI: http://d-scholarship.pitt.edu/id/eprint/13882

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