Interferon regulatory factor 1 priming of tumour-derived exosomes enhances the antitumour immune response

Background: Tumour-derived exosomes (TEXs) have a potential for application in cancer vaccines. Whether TEXs after induction by interferon regulatory factor 1 (IRF-1) are capable of enhancing the antitumour response remains to be determined. Methods: Exosomes released by tumour cells infected with IRF-1-expressing adenovirus (IRF-1-Exo) or treated with interferon- γ (IFN-Exo) were isolated via ultracentrifugation. The IRF-1 target proteins IL-15R α and MHC class I (MHC-I) were analysed by western blot. Exosomes along with CpG adjuvant were injected into tumour models to assess the antitumour effects. Tumours were harvested for immunofluorescence staining. Splenocytes from tumour-bearing mice were co-cultured with tumour cells. The IFN γ -positive and granzyme B-positive CD8 α + splenocyte cells were quantified by flow cytometry. Results: The IRF-1-Exo or IFN-Exo displayed increased IL-15R α and MHC-I expression. Injection of IRF-1-Exo or IFN-Exo combined with CpG had improved antitumour effects in mice. This effect may be a result of increased infiltration of tumours by CD4+ and CD8 α + T cells. Antibody-mediated depletion of CD4+ or CD8+ T cells abrogated the antitumour effects. Splenocytes isolated from CpG+IRF-1-Exo-injected Hepa 1–6 tumour mice had increased IFN γ -positive and granzyme B-positive CD8+ cells after co-culturing with Hepa 1–6 cells as compared with MC38 cells. Conclusions: The IRF-1 priming of TEXs enhances antitumour immune response.