microRNA-155 deficiency impairs dendritic cell function in breast cancer.
microRNA-155 deficiency impairs dendritic cell function in breast cancer.
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DOI：
10.1080/2162402x.2016.1232223
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发表时间：
2016
期刊：
影响因子：
7.2
通讯作者：
Fan D
中科院分区：
文献类型：
--
作者：
Wang J;Iwanowycz S;Yu F;Jia X;Leng S;Wang Y;Li W;Huang S;Ai W;Fan D
在抗肿瘤免疫中，树突状细胞（DC）捕获、加工并将肿瘤抗原呈递给T细胞，从而引发杀肿瘤反应。然而，DC由于暴露于肿瘤微环境（TME）而经常功能失调，导致肿瘤逃避免疫监视。本文报道了microRNA-155（miR-155）在乳腺癌中调节DC功能的重要作用。宿主miR-155缺陷增强了小鼠乳腺癌的生长，伴随着肿瘤和引流淋巴结中DC的减少。DC中的miR-155缺陷损害了它们的成熟、迁移能力、细胞因子产生和活化T细胞的能力。我们证明miR-155通过表观遗传学调节CCR 7表达来调节DC迁移。此外，发现TME中丰富的两种细胞因子IL-6和IL-10通过抑制miR-155表达来损害DC成熟。此外，动物研究表明，缺乏miR-155会降低基于DC的乳腺癌免疫疗法的有效性。总之，这些发现表明miR-155是乳腺癌中DC功能的主要调节因子，包括成熟、细胞因子分泌、向淋巴结迁移和T细胞活化。这些结果表明，提高单个microRNA（miR-155）的表达可能会显着提高基于DC的乳腺癌免疫疗法的疗效。
In antitumor immunity, dendritic cells (DCs) capture, process, and present tumor antigens to T cells, initiating a tumoricidal response. However, DCs are often dysfunctional due to their exposure to the tumor microenvironment (TME), leading to tumor escape from immune surveillance. Here, a vital role of microRNA-155 (miR-155) in regulating the function of DCs in breast cancer is reported. Host miR-155 deficiency enhanced breast cancer growth in mice, accompanied by reduced DCs in the tumors and draining lymph nodes. miR-155 deficiency in DCs impaired their maturation, migration ability, cytokine production, and the ability to activate T cells. We demonstrate that miR-155 regulates DC migration through epigenetic modulation of CCR7 expression. Moreover, IL-6 and IL-10, two cytokines abundant in the TME, are found to impair DC maturation by suppressing miR-155 expression. Furthermore, animal studies show that a lack of miR-155 diminishes the effectiveness of DC-based immunotherapy for breast cancer. In conclusion, these findings suggest that miR-155 is a master regulator of DC function in breast cancer, including maturation, cytokine secretion, migration toward lymph nodes, and activation of T-cells. These results suggest that boosting the expression of a single microRNA, miR-155, may significantly improve the efficacy of DC-based immunotherapies for breast cancer.