Activation of dendritic cells by targeted DNA: a potential addition to the armamentarium for anti-cancer immunotherapy
In the past decade, remarkable progress has been made in immunotherapy against cancer. Specifically, the introduction of immune checkpoint inhibitors has revolutionized the field. However, many patients are unable to benefit significantly from this treatment option. One of the major reasons for this is most likely the absence of an adequate tumor-specific T cell response in these patients. A way to circumvent this problem might be to combine immune checkpoint inhibitor treatment with new strategies to activate tumor-specific T cells. One such strategy could be to activate and mature dendritic cells in situ. Dendritic cells carry an array of external and internal pattern recognition receptors that induce cell activation and maturation when interacting with their corresponding damage-associated or pathogen-associated molecular patterns (DAMPs or PAMPs). Targeting such molecular patterns directly to dendritic cells might be a way to evoke stronger immune responses. Here, we review our recent findings using antibody-targeted DNA. We summarize the results from our experiments showing that dendritic cells can be actively targeted in vivo through the αXβ2 integrin subunit CD11c, and that DNA delivered through this receptor in vitro leads to maturation of dendritic cells via the cytosolic cGAS/STING DNA-sensing pathway.
KeywordsCancer Cancer immunotherapy Dendritic cells STING PIVAC 18
Classical type 1 dendritic cell
Classical type 2 dendritic cell
Cyclic GMP–AMP synthase
Complement receptor 4
Damage-associated molecular pattern
Interferon regulatory factor 3
Monocyte-derived dendritic cell
Pathogen-associated molecular pattern
Plasmacytoid dendritic cell
Pattern recognition receptor
Stimulator of interferon genes
TANK-binding kinase 1
Marlene Fyrstenberg Laursen, Emil Kofod-Olsen and Ralf Agger all contributed equally to the writing of the manuscript.
The support for our research from The Danish Cancer Society (Grant No. A10193), Dansk Kræftforskningsfond, The Andersen-Isted Foundation, The Else og Mogens Wedell-Wedellsborgs Foundation, Familien Erichsens Mindefond, Fabrikant Einar Willumsens Mindefond and The Pedersen Charity Foundation, Vaduz, Liechtenstein is gratefully acknowledged.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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