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首页> 外文期刊>International journal of hyperthermia: The official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group >Induction of a tumour-specific CTL response by exosomes isolated from heat-treated malignant ascites of gastric cancer patients
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Induction of a tumour-specific CTL response by exosomes isolated from heat-treated malignant ascites of gastric cancer patients

机译：从胃癌患者恶性腹水的热处理中分离的外泌体诱导肿瘤特异性CTL反应

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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.
机译：目的：肿瘤细胞来源的外来体可能代表一种新型的癌症疫苗。然而，已经证明衍生自肿瘤细胞的外泌体的免疫原性很差。因此，在本研究中，评估了从胃癌患者获得的恶性腹水对外泌体进行热处理后的外泌体免疫原性。材料和方法：采用连续离心和蔗糖梯度超速离心法，从胃癌患者的经热处理和未经治疗的恶性腹水中分离出肿瘤来源的外泌体。接下来，进行体外实验以研究热处理对外泌体免疫原性的影响。结果：发现胃癌患者恶性腹水经热处理后的外泌体（HS外泌体）中所含热休克蛋白Hsp70和Hsp60的浓度高于胃癌患者未经治疗的恶性腹水所致的外泌体。额外的体外研究表明，源自经过热处理的恶性腹水的外泌体能够促进树突状细胞（DC）成熟并诱导肿瘤特异性细胞毒性T淋巴细胞（CTL）反应。结论：总的来说，这些结果表明暴露于热应激可以改善从胃癌患者的恶性腹水获得的外泌体的免疫原性。

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