Integrated Nanovaccine with MicroRNA-148a Inhibition Reprograms Tumor-Associated Dendritic Cells by Modulating miR-148a/DNMT1/SOCS1 Axis.
文献类型：期刊论文
| 作者 | Liu, Lanlan; Yi, Huqiang; Wang, Ce; He, Huamei; Li, Ping; Pan, Hong; Sheng, Nan; Ji, Manyi; Cai, Lintao; Ma, Yifan |
| 刊名 | JOURNAL OF IMMUNOLOGY
 |
| 出版日期 | 2016 |
| 英文摘要 | Immunosuppressive tumor-associated dendritic cells (TADCs) are potential targets for cancer therapy. However, their poor responsiveness to TLR stimulation is a major obstacle for achieving successful cancer immunotherapy. In the current study, we reported a dysregulated miR-148a/DNA methyltransferase (DNMT) 1/suppressor of cytokine signaling (SOCS) 1 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 polyinosinic-polycytidylic acid (poly I:C) or LPS-induced dendritic cell maturation through directly suppressing DNMT1 gene, which consequently led to the hypomethylation and upregulation 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 coencapsulated with poly I:C and OVA by cationic polypeptide micelles to generate integrated polypeptide micelle/poly I:C (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/SOCS1axis in the spleen, but also significantly increased mature dendritic cells both in the spleen and in tumor microenvironment. Moreover, PMP/OVA/148ai ameliorated tumor immunosuppression through reducing regulatory T cells and myeloid-derived suppressor cells, thereby leading to potent anticancer immune responses and robust tumor regression with prolonged survival. This study proposes a nanovaccine-based immunogene therapy with the integration of miR-148a inhibition and TLR3 stimulation as a novel therapeutic approach to boost anticancer immunity by reprogramming TADCs in vivo. |
| 收录类别 | SCI |
| 原文出处 | http://www.jimmunol.org/content/197/4/1231.short |
| 语种 | 英语 |
| 源URL | [http://ir.siat.ac.cn:8080/handle/172644/10696]  |
| 专题 | 深圳先进技术研究院_医药所 |
| 作者单位 | JOURNAL OF IMMUNOLOGY |
| 推荐引用方式 GB/T 7714 | Liu, Lanlan,Yi, Huqiang,Wang, Ce,et al. Integrated Nanovaccine with MicroRNA-148a Inhibition Reprograms Tumor-Associated Dendritic Cells by Modulating miR-148a/DNMT1/SOCS1 Axis.[J]. JOURNAL OF IMMUNOLOGY,2016. |
| APA | Liu, Lanlan.,Yi, Huqiang.,Wang, Ce.,He, Huamei.,Li, Ping.,...&Ma, Yifan.(2016).Integrated Nanovaccine with MicroRNA-148a Inhibition Reprograms Tumor-Associated Dendritic Cells by Modulating miR-148a/DNMT1/SOCS1 Axis..JOURNAL OF IMMUNOLOGY. |
| MLA | Liu, Lanlan,et al."Integrated Nanovaccine with MicroRNA-148a Inhibition Reprograms Tumor-Associated Dendritic Cells by Modulating miR-148a/DNMT1/SOCS1 Axis.".JOURNAL OF IMMUNOLOGY (2016). |
入库方式： OAI收割
来源：深圳先进技术研究院
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