Overexpression of microRNA-155 enhances the efficacy of dendritic cell vaccine against breast cancer

ABSTRACT

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.

KEYWORDS:

• Microrna-155
• dendritic cell
• vaccine
• breast cancer
• immune therapy

Abbreviations

CSFE	=	Carboxyfluorescein diacetate succinimidyl ester
DC	=	Dendritic cell
miR-155	=	microRNA-155
miR-155−/-	=	bic/miR-155 knockout
miR-155tg	=	microRNA-155 transgenic
qPCR	=	Quantitative real-time RT-PCR
TCM	=	Tumor cell conditioned media
TME	=	Tumor microenvironment

Author contribution

DF and JW designed the study; JH, FW, QL, FS, YW and US performed the experiments; FW, JW, JH and DF wrote the manuscript draft; WA, HC, and ML helped in interpretation of the data and manuscript writing.

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This work was supported by NIH grants R01CA218578 and R21CA216230 (to DF). Johnie Hodge has been supported by the Susan G. Komen trainee program (GTDR17500160).