Journal
IMMUNOLOGY
Volume 154, Issue 1, Pages 132-143Publisher
WILEY
DOI: 10.1111/imm.12874
Keywords
exosomes; heat stress; IL-6; Th17; T-regs
Categories
Funding
- Natural Science Foundation of Zhejiang Province [LY14H160011]
- National Natural Science Foundation of China [31400750]
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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.
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