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MicroRNA-155 deficiency impairs dendritic cell function in breast cancer.

ABSTRACT: 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.

SUBMITTER: Wang J

PROVIDER: S-EPMC5139631 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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microRNA-155 deficiency impairs dendritic cell function in breast cancer.

Wang Junfeng J Iwanowycz Stephen S Yu Fang F Jia Xuemei X Leng Shuilong S Wang Yuzhen Y Li Wei W Huang Shiang S Ai Walden W Fan Daping D

Oncoimmunology 20160909 11

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 ...[more]

PMID: 27999745

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MicroRNA-155 deficiency impairs dendritic cell function in breast cancer.

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microRNA-155 deficiency impairs dendritic cell function in breast cancer.

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