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

Plasma-derived MHC class II+ exosomes from tumor-bearing mice suppress tumor antigen-specific immune responses.
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DOI:
10.1002/eji.201141978
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发表时间:
2012-07
影响因子:
5.4
通讯作者:
Robbins, Paul D.
Robbins, Paul D.
中科院分区:
医学3区
文献类型:
--
作者:
Yang, Chenjie;Ruffner, Melanie A.;Kim, Seon-Hee;Robbins, Paul D.

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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 response 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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