MicroRNA 155 (miR-155) plays important roles in the regulation of the development and functions of a variety of immune cells. We previously revealed a vital role of miR-155 in regulating the function of dendritic cells (DCs) in breast cancer. miR-155 deficiency in DCs impaired their maturation, migration, cytokine production, and ability to activate T cells. In the current study, to exploit the therapeutic value of miR-155 for breast cancer, we examined the impact of overexpression of miR-155 on antitumor responses generated by DC vaccines. We boosted miR-155 expression in DCs by generating a miR-155 transgenic mouse strain (miR-155tg) or using lentivirus transduction. DCs overexpressing miR-155 exhibited enhanced functions in response to tumor antigens. Using miR-155 overexpressing DCs, we generated a DC vaccine and found that the vaccine resulted in enhanced antitumor immunity against established breast cancers in mice, demonstrated by increased effector T cells in the mice, suppressed tumor growth, and drastically reduced lung metastasis. Our current study suggests that in future DC vaccine development for breast cancer or other solid tumors, introducing forced miR155 overexpression in DCs via various approaches such as viral transduction or nanoparticle delivery, as well as including other adjuvant agents such as TLR ligands or immune stimulating cytokines, may unleash the full therapeutic potential of the DC vaccines.

中文翻译：

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microRNA-155的过表达增强了树突状细胞疫苗抗乳腺癌的功效。

MicroRNA 155（miR-155）在调节各种免疫细胞的发育和功能中起重要作用。我们先前揭示了miR-155在调节乳腺癌中树突状细胞（DC）功能方面的重要作用。DC中的miR-155缺陷会损害其成熟，迁移，细胞因子产生以及激活T细胞的能力。在当前的研究中，为了开发miR-155对乳腺癌的治疗价值，我们检查了miR-155的过表达对DC疫苗产生的抗肿瘤反应的影响。我们通过产生miR-155转基因小鼠品系（miR-155tg）或使用慢病毒转导来增强DC中的miR-155表达。过度表达miR-155的DC响应肿瘤抗原表现出增强的功能。使用miR-155过表达的DC，我们制备了DC疫苗，发现该疫苗可增强小鼠对已建立的乳腺癌的抗肿瘤免疫力，这可通过小鼠效应T细胞的增加，肿瘤生长的抑制和肺转移的急剧减少来证明。我们目前的研究表明，在未来针对乳腺癌或其他实体瘤的DC疫苗开发中，会通过各种方法（例如病毒转导或纳米颗粒递送）以及包括其他佐剂（例如TLR配体或免疫刺激性细胞因子）在DC中引入强迫性miR155过表达。可能会释放出DC疫苗的全部治疗潜力。