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	Integrated nanovaccine with microRNA-148a inhibition reprograms tumor-associated dendritic cells by modulating miR-148a/DNMT1/SOCS1 axis
	Lanlan Liu; Yifan Ma; Lintao Cai
	2016
会议名称	The 14th International Symposium on Dendritic Cells
会议地点	中国上海
英文摘要	Immunosuppressive tumor-associated dendritic cells (TADCs) are potential targets for cancer therapy. However, their poor responsiveness to toll-like receptor (TLR) stimulation is a major obstacle for achieving successful cancer immunotherapy. In the present study, we reported a dysregulated miR-148a/DNMT1/SOCS1 axis as a unique mechanism for dampened TLR stimulation in TADCs. The results showed that aberrantly elevated miR-148a in bone marrow derived-TADC (BM-TADC) abolished poly I:C or LPS-induced DC maturation through directly suppressing DNMT1 gene, which consequently led to the hypomethylation and up-regulation of SOCS1, the suppressor of TLR signaling. In contrast, miR-148a inhibitor (miR-148ai) effectively rescued the expression of DNMT1 and decreased SOCS1 in BM-TADCs, thereby recovering their sensitivity to TLR3 or TLR4 stimulation. To further reprogram TADCs in vivo, miR-148ai was co-encapsulated with poly I:C and OVA by cationic polypeptide micelles (PM) to generate integrated PMP/OVA/148ai nanovaccine, which was designed to simultaneously inhibit miR-148a and activate TLR3 signaling in TADCs. The immunization of PMP/OVA/148ai nanovaccine not only effectively modulated the miR-148a/DNMT1/SOCS1 axis in the spleen, but also significantly increased mature DCs both in the spleen and in tumor microenvironment. Moreover, PMP/OVA/148ai ameliorated tumor immunosuppression through reducing Treg cells and MDSCs, thereby leading to potent anti-cancer immune responses and robust tumor regression with prolonged survival. This study proposes a nanovaccine-based immuno-gene therapy with the integration of miR-148a inhibition and TLR3 stimulation as a novel therapeutic approach to boost anti-cancer immunity by reprogramming TADCs in vivo.
收录类别	其他
语种	英语
内容类型	会议论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/10821]
专题	深圳先进技术研究院_医药所
作者单位	2016
推荐引用方式 GB/T 7714	Lanlan Liu,Yifan Ma,Lintao Cai. Integrated nanovaccine with microRNA-148a inhibition reprograms tumor-associated dendritic cells by modulating miR-148a/DNMT1/SOCS1 axis[C]. 见:The 14th International Symposium on Dendritic Cells. 中国上海.

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