title: Exosomal cancer immunotherapy is independent of MHC molecules on exosomes.
abstract: 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 antigen-specific 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.
authors.affiliation: Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institute, and Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hiltbrunner
authors.affiliation: Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institute, and Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Pia
authors.initials: P
authors.lastname: Larssen
authors.affiliation: Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institute, and Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Eldh
authors.affiliation: Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institute, and Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Martinez-Bravo
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: Arnika K
authors.initials: AK
authors.lastname: Wagner
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: Mikael C I
authors.initials: MC
authors.lastname: Karlsson
authors.affiliation: Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institute, and Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Gabrielsson
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D006649:Histocompatibility Antigens / Q000378:metabolism*; D007167:Immunotherapy / Q000379:methods*; D008264:Macrophages / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D010641:Phenotype; D015854:Up-Regulation
chemical_list: D006649:Histocompatibility Antigens
keywords: MHC class I; cancer; exosomes; extracellular vesicles; immunotherapy