Journal
OncoImmunology
Volume 5, Issue 11, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2016.1232223
Keywords
Breast cancer; CCR7; dendritic cell; epigenetic modulation; Immunotherapy; microRNA-155; tumor microenvironment
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Funding
- NIH [R01HL116626, AT003961-8455]
- National Natural Science Foundation of China [3097112]
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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.
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