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Cancer Immunology, Immunotherapy

, Volume 68, Issue 11, pp 1875–1880 | Cite as

Activation of dendritic cells by targeted DNA: a potential addition to the armamentarium for anti-cancer immunotherapy

  • Marlene Fyrstenberg Laursen
  • Emil Kofod-Olsen
  • Ralf AggerEmail author
Focussed Research Review

Abstract

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.

Keywords

Cancer Cancer immunotherapy Dendritic cells STING PIVAC 18 

Abbreviations

cDC1

Classical type 1 dendritic cell

cDC2

Classical type 2 dendritic cell

CDN

Cyclic di-nucleotide

cGAMP

Cyclic GMP–AMP

cGAS

Cyclic GMP–AMP synthase

CR4

Complement receptor 4

DAMP

Damage-associated molecular pattern

ER

Endoplasmic reticulum

IRF3

Interferon regulatory factor 3

moDC

Monocyte-derived dendritic cell

PAMP

Pathogen-associated molecular pattern

pDC

Plasmacytoid dendritic cell

PRR

Pattern recognition receptor

STING

Stimulator of interferon genes

TBK1

TANK-binding kinase 1

Notes

Author contributions

Marlene Fyrstenberg Laursen, Emil Kofod-Olsen and Ralf Agger all contributed equally to the writing of the manuscript.

Funding

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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Laboratory of Immunology, Department of Health Science and TechnologyAalborg UniversityAalborgDenmark

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