期刊
ONCOTARGET
卷 7, 期 25, 页码 38707-38717出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9585
关键词
exosomes; immunotherapy; MHC class I; extracellular vesicles; cancer
资金
- Swedish Medical Research Council VR [K2013-67X-15242-10-5]
- Swedish Cancer Foundation [2013/867]
- Cancer Research Foundations of Radiumhemmet [131082]
- Stockholm County Council [20140405]
- Swedish Heart-Lung Foundation [20140497, 20140711, 20130551]
- Centre for Allergy Research
- ChAMP consortium at the Karolinska Institute
- ChAMP consortium at the Hesselman Foundation
- ChAMP consortium at the KID grant of the Karolinska Institute
Peptide-loaded exosomes are promising cancer treatment vehicles; however, moderate T cell responses in human clinical trials indicate a need to further understand exosome-induced immunity. We previously demonstrated that antigen-loaded exosomes carry whole protein antigens and require B cells for inducing antigenspecific T cells. Therefore, we investigated the relative importance of exosomal major histocompatibility complex (MHC) class I for the induction of antigen-specific T cell responses and tumour protection. We show that ovalbumin-loaded dendritic cell-derived exosomes from MHCI-/- mice induce antigen-specific T cells at the same magnitude as wild type exosomes. Furthermore, exosomes lacking MHC class I, as well as exosomes with both MHC class I and II mismatch, induced tumour infiltrating T cells and increased overall survival to the same extent as syngeneic exosomes in B16 melanoma. In conclusion, T cell responses are independent of exosomal MHC/ peptide complexes if whole antigen is present. This establishes the prospective of using impersonalised exosomes, and will greatly increase the feasibility of designing exosome-based vaccines or therapeutic approaches in humans.
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