Upregulation of microRNA-155 Enhanced Migration and Function of Dendritic Cells in Three-dimensional Breast Cancer Microenvironment
Upregulation of microRNA-155 Enhanced Migration and Function of Dendritic Cells in Three-dimensional Breast Cancer Microenvironment
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上调 microRNA-155 增强三维乳腺癌微环境中树突状细胞的迁移和功能
DOI：
10.1080/08820139.2020.1801721
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发表时间：
2020-08
影响因子：
2.8
通讯作者：
Jing Jie
中科院分区：
文献类型：
--
作者：
Pengxiang Yang;Xingjian Cao;Huilong Cai;Xiang Chen;Yihua Zhu;Yue Yang;Weiwei An;Jing Jie
摘要背景：树突状细胞（Dendritic cells，DC）在诱导和调节免疫应答中起重要作用，包括激活效应T淋巴细胞以根除癌症。然而，肿瘤微环境（TME）往往会导致DC功能障碍，由于其不成熟的状态。MicroRNA-155（miR-155）是一种典型的多功能基因调控因子，与免疫系统发育、免疫细胞活化和分化有关。方法：在这项研究中，一个三维TME模型，密切模仿乳腺癌的微环境制备。使用慢病毒构建miR-155过表达载体和对照载体。通过qRT-PCR测定miR-155的相对表达。通过活-死染色和流式细胞术分析细胞活力、抗原摄取和细胞表面标志物表达。transwell法检测骨髓来源DC的迁移能力。混合淋巴细胞培养试验用于评估T细胞特异性增殖。通过ELISA测定细胞因子水平。结果：TME可抑制DC中miR-155的表达。此外，上调miR-155增强了迁移能力、抗原摄取并提高了成熟DCs标志物CD 80和MHCII的表达。更重要的是，miR-155在DC中的过表达显著诱导T细胞增殖以及IFN-γ和IL-2的分泌。结论：MiR-155是一种潜在的分子调节剂，可提高基于DC的肿瘤免疫治疗的疗效。
ABSTRACT Background: Dendritic cells (DCs) play an essential role in the induction and regulation of immune responses, including the activation of effector T lymphocytes for the eradication of cancers. However, the tumor microenvironment (TME) often leads to DCs dysfunction due to their immature state. MicroRNA-155 (miR-155) has emerged as a typical multifunctional gene regulator associated with immune system development and immune cell activation and differentiation. Methods: In this study, a three-dimensional TME model that closely mimics the microenvironment of breast cancer was prepared. MiR-155 overexpression and control vectors were constructed using lentivirus. The relative expression of miR-155 was determined by qRT-PCR. Cell viability, antigen uptake and cell surface marker expression were analyzed by live-dead staining and flow cytometry. The migration ability of bone marrow-derived DCs (BMDCs) was qualified by transwell assay. A mixed lymphocyte culture assay was used to assess T cell-specific proliferation. Cytokine levels were determined by ELISA. Results: We found that the expression of miR-155 in DCs was inhibited by the TME. Furthermore, upregulation of miR-155 enhanced the migration ability, uptake of antigen and elevated the expression of the mature DCs markers CD80 and MHCII. More importantly, overexpression of miR-155 in DCs significantly induced T cell proliferation and IFN-γ and IL-2 secretion. Conclusion: MiR-155 is a potential molecular regulator that may improve the efficacy of DCs-based tumor immunotherapy.
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DOI：
10.1002/psc.2940
发表时间：
2017-02
期刊：
Journal of peptide science : an official publication of the European Peptide Society
影响因子：
--
作者：
Markey A;Workman VL;Bruce IA;Woolford TJ;Derby B;Miller AF;Cartmell SH;Saiani A
通讯作者：
Saiani A
影响因子：
5.6
作者：
Jie J;Zhang Y;Zhou H;Zhai X;Zhang N;Yuan H;Ni W;Tai G
通讯作者：
Tai G
影响因子：
4.4
作者：
Y. Nakagawa;Yasuyuki Negishi;Masumi Shimizu;M. Takahashi;M. Ichikawa;Hidemi Takahashi
通讯作者：
Y. Nakagawa;Yasuyuki Negishi;Masumi Shimizu;M. Takahashi;M. Ichikawa;Hidemi Takahashi
影响因子：
7.2
作者：
Wang J;Iwanowycz S;Yu F;Jia X;Leng S;Wang Y;Li W;Huang S;Ai W;Fan D
通讯作者：
Fan D
影响因子：
2.2
作者：
Lu Yang;Rui Li;S. Xiang;Weihua Xiao
通讯作者：
Lu Yang;Rui Li;S. Xiang;Weihua Xiao