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

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 t...

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Main Authors: Chenjie Yang, Seon-Hee Kim, Nicole R Bianco, Paul D Robbins
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3149056?pdf=render
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author Chenjie Yang
Seon-Hee Kim
Nicole R Bianco
Paul D Robbins
author_facet Chenjie Yang
Seon-Hee Kim
Nicole R Bianco
Paul D Robbins
author_sort Chenjie Yang
collection DOAJ
description 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.
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spelling doaj.art-0d9c2dfe61a84b51b857aeab2332fe792022-12-22T01:15:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2251710.1371/journal.pone.0022517Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model.Chenjie YangSeon-Hee KimNicole R BiancoPaul D RobbinsExosomes 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.http://europepmc.org/articles/PMC3149056?pdf=render
spellingShingle Chenjie Yang
Seon-Hee Kim
Nicole R Bianco
Paul D Robbins
Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model.
PLoS ONE
title Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model.
title_full Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model.
title_fullStr Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model.
title_full_unstemmed Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model.
title_short Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model.
title_sort tumor derived exosomes confer antigen specific immunosuppression in a murine delayed type hypersensitivity model
url http://europepmc.org/articles/PMC3149056?pdf=render
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AT nicolerbianco tumorderivedexosomesconferantigenspecificimmunosuppressioninamurinedelayedtypehypersensitivitymodel
AT pauldrobbins tumorderivedexosomesconferantigenspecificimmunosuppressioninamurinedelayedtypehypersensitivitymodel