肿瘤细胞来源的exosomes通过HSP70/TLR/IL-6途径介导人与小鼠树突状细胞促肿瘤转移作用的研究

Dendritic cells (DCs) can initiate robust and long-lasting antitumor immunity. However, tumor mciroenvironment can also educate DCs and convert them into tumor promoter. Exosomes are small vesicles with bilayer membrane structure released from all kinds of live cells. Tumor-derived exosomes (TEXs) have been reported to induce antitumor immunity. But TEXs are also demonstrated to promote tumor progression. It remains unknown whether TEXs possess the effect of stimulation and suppression of antitumor immunity in the same time. In our previous study, we find that TEXs can promote the maturation and activation of DCs, inflammatory mediators secretion of DCs and TLR-signaling activation of DCs which is probably related to HSP70 carried by TEXs. TEXs activated DCs can promote tumor cell invasion depending on autocrine of IL-6. In this project, we will further study whether TEXs can promote tumor metastasis in a HSP70/TLR/IL-6-dependent manner. The results of this project will reveal not only a novel mechanism of tumor escape mediated by DCs but the ultimate effect of TEXs on the tumor progression that possess the effect of stimulation and suppression of antitumor immunity in the same time.

树突状细胞（Dendritic cells, DCs）能激发机体强大、持久的抗肿瘤免疫反应。但肿瘤细胞也可"驯化"DCs，使其促进肿瘤进展。Exosomes是各种活细胞分泌的膜性囊泡，肿瘤细胞来源的exosomes（Tumor-derived exosomes, TEXs）可诱导机体抗肿瘤免疫，但研究也表明，TEXs可促进肿瘤进展。对于同一TEXs是否同时具有免疫激活和抑制功能尚无相关报道。我们研究结发现，TEXs能促进DCs的成熟与活化；炎症介质的分泌；Toll样信号的活化，并使DCs依赖自分泌IL-6促进肿瘤侵袭。TEXs含有的HSP70可能介导DCs Toll样信号的活化。本项目拟深入研究TEXs是否可通过HSP70/TLR/IL-6途径介导DCs促肿瘤转移作用。该项目的研究成果，将揭示DCs免疫逃逸的一种新机制，阐明同时拥有免疫激活和抑制功能的TEXs在肿瘤进展中的最终作用。

树突状细胞（Dendritic cells, DCs）能激发机体强大、持久的抗肿瘤免疫反应。但肿瘤细胞也可"驯化"DCs，使其促进肿瘤进展。Exosomes是各种活细胞分泌的膜性囊泡，肿瘤细胞来源的exosomes（Tumor-derived exosomes, TEXs）可诱导机体抗肿瘤免疫，但研究也表明，TEXs可促进肿瘤进展。对于同一TEXs是否同时具有免疫激活和抑制功能尚无相关报道。我们研究结发现，TEXs能促进DCs的成熟与活化；炎症介质的分泌；Toll样信号的活化，并使DCs依赖自分泌IL-6促进肿瘤侵袭。TEXs含有的HSP70可能介导DCs Toll样信号的活化。本项目拟深入研究TEXs是否可通过HSP70/TLR/IL-6途径介导DCs促肿瘤转移作用。该项目的研究成果，将揭示DCs免疫逃逸的一种新机制，阐明同时拥有免疫激活和抑制功能的TEXs在肿瘤进展中的最终作用。