title: 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.
authors.affiliation: Centre for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC, USA.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine , Columbia, SC, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Iwanowycz
authors.affiliation: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine , Columbia, SC, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine , Columbia, SC, USA.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine , Columbia, SC, USA.
authors.forename: Shuilong
authors.initials: S
authors.lastname: Leng
authors.affiliation: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine , Columbia, SC, USA.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine , Columbia, SC, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Centre for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China.
authors.forename: Shiang
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine , Columbia, SC, USA.
authors.forename: Walden
authors.initials: W
authors.lastname: Ai
authors.affiliation: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine , Columbia, SC, USA.
authors.forename: Daping
authors.initials: D
authors.lastname: Fan
keywords: Breast cancer; CCR7; Immunotherapy; dendritic cell; epigenetic modulation; microRNA-155; tumor microenvironment