期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 42, 期 7, 页码 1778-1784出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201141978
关键词
Exosomes; Hypersensitivity; Immune regulation; Tolerance; Tumors
类别
资金
- Department of Defense [17-03-1-0488, 17-03-0412]
- National Institutes of Health [U01 NS058451, P30 AG024827, P01 CA100327, R01 AR051456, R21 AG033907]
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.
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