Plasma-derived MHC class II+ exosomes from tumor-bearing mice suppress tumor antigen-specific immune responses

Chenjie Yang, Melanie A. Ruffner, Seon Hee Kim, Paul D. Robbins

Research output: Contribution to journalArticle

33 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1778-1784
Number of pages7
JournalEuropean Journal of Immunology
Volume42
Issue number7
DOIs
StatePublished - Jul 1 2012
Externally publishedYes

Keywords

  • Exosomes
  • Hypersensitivity
  • Immune regulation
  • Tolerance
  • Tumors

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