Induction of a tumour-specific CTL response by exosomes isolated from heat-treated malignant ascites of gastric cancer patients.

摘要

PURPOSE: Tumour cell-derived exosomes may represent a novel type of cancer vaccine. However, the immunogenicity of exosomes derived from tumour cells has been shown to be poor. Therefore, in this study, exosome immunogenicity following heat treatment of exosomes from malignant ascites obtained from gastric cancer patients was evaluated. MATERIALS AND METHODS: Tumour-derived exosomes were isolated from heat-treated and untreated malignant ascites of gastric cancer patients using serial centrifugation and sucrose gradient ultracentrifugation. Next, in vitro experiments were performed to investigate the influence of heat treatment on exosome immunogenicity. RESULTS: Exosomes from heat-treated malignant ascites of gastric cancer patients (HS exosomes) were found to contain higher concentrations of heat shock proteins, Hsp70 and Hsp60, than exosomes derived from untreated malignant ascites obtained from gastric cancer patients. Additional in vitro studies suggest that exosomes derived from heat-treated malignant ascites are able to promote dendritic cell (DC) maturation and induce a tumour-specific cytotoxic T lymphocyte (CTL) response. CONCLUSIONS: Overall, these results demonstrate that exposure to heat stress can improve the immunogenicity of exosomes obtained from malignant ascites of gastric cancer patients.