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Exosomes from heat‐stressed tumour cells inhibit tumour growth by converting regulatory T cells to Th17 cells via IL‐6
Author(s) -
Guo Danfeng,
Chen Yinghu,
Wang Shoujie,
Yu Lei,
Shen Yingying,
Zhong Haijun,
Yang Yunshan
Publication year - 2018
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12874
Subject(s) - microvesicles , secretion , in vitro , peripheral blood mononuclear cell , immune system , cancer research , hyperthermia , biology , microbiology and biotechnology , t cell , heat shock protein , chemistry , immunology , endocrinology , microrna , biochemistry , gene , paleontology
Summary Exosomes derived from heat‐stressed tumour cells (HS‐TEXs), which contain abundant heat shock protein (HSP) 70, strongly induce antitumour immune responses. HSP70‐induced interleukin (IL)‐6 promotes IL‐17 expression and causes rejection of established prostate tumours. However, it remains unclear whether HS‐TEXs exhibit antitumour effects by converting regulatory T cells (T regs ) into T helper type 17 (Th17) cells. In this study, we found that compared with TEXs, HS‐TEXs were more potent in stimulating secretion of IL‐6 from dendritic cells. In vitro , IL‐6 blocked tumour cell‐derived transforming growth factor beta 1‐induced T reg differentiation and promoted Th17 cell differentiation. HS‐TEXs exerted strong antitumour effects, converting T regs into Th17 cells with high efficiency, a process that was entirely dependent upon IL‐6. Neutralization of IL‐17 completely abolished the antitumour effect of TEXs, but only partially inhibited that of HS‐TEXs. In addition, we found higher levels of IL‐6 and IL‐17 in serum from tumour patients treated with hyperthermia, and an increase in Th17 cells and a decrease in T regs was detected in peripheral blood mononuclear cells isolated from these patients after hyperthermia. Therefore, our results demonstrate that HS‐TEXs possess a powerful capacity to convert immunosuppressive T regs into Th17 cells via IL‐6, which contributes to their potent antitumour effect.