NF-κB activation triggers NK-cell stimulation by monocyte-derived dendritic cells.

Bosch NC, Voll RE, Voskens CJ, Gross S, Seliger B, Schuler G, Schaft N, Dörrie J (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Therapeutic Advances in Medical Oncology SAGE Publications

Book Volume: 11

Pages Range: 1758835919891622

DOI: 10.1177/1758835919891622

Abstract

Background: In therapeutic cancer vaccination, monocyte-derived dendritic cells (moDCs) efficiently activate specific T-cell responses; however, optimizing the activation of innate immune cells could support and improve the antitumor effects. A major disadvantage of moDCs matured with the standard cytokine cocktail (consisting of IL-1 beta, IL-6, TNF alpha, and PGE(2)) is their inability to secrete IL-12p70. IL-12 prominently activates natural killer (NK) cells, which are crucial in innate antitumor immunity, as they act as helper cells for the induction of a cytotoxic T lymphocyte (CTL) response and are also able to directly kill the tumor. Methods: Previously we have shown that triggering the NF-kappa B pathway in moDCs by transfection of mRNA encoding constitutively active IKK beta (caIKK beta) led to IL-12p70 secretion and improved the dendritic cells' capability to activate and expand CTLs with a memory-like phenotype. In this study, we examined whether such dendritic cells could activate autologous NK cells. Results: moDCs matured with the standard cytokine cocktail followed by transfection with the caIKK beta-RNA were able to activate autologous NK cells, detected by the upregulation of CD54, CD69, and CD25 on the NK cells, their ability to secrete IFN gamma, and their high lytic activity. Moreover, the ability of NK-cell activation was not diminished by simultaneous T-cell activation. Conclusion: The capacity of caIKK beta-DCs to activate both the adaptive and innate immune response indicates an enhanced potential for clinical efficacy.

Authors with CRIS profile

Gerold Schuler Lehrstuhl für Haut- und Geschlechtskrankheiten Niels Schaft Department of Dermatology Jan Dörrie Department of Dermatology

Involved external institutions

Martin-Luther-Universität Halle-Wittenberg (MLU) DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE)

How to cite

APA:

Bosch, N.C., Voll, R.E., Voskens, C.J., Gross, S., Seliger, B., Schuler, G.,... Dörrie, J. (2019). NF-κB activation triggers NK-cell stimulation by monocyte-derived dendritic cells. Therapeutic Advances in Medical Oncology, 11, 1758835919891622. https://doi.org/10.1177/1758835919891622

MLA:

Bosch, Naomi C., et al. "NF-κB activation triggers NK-cell stimulation by monocyte-derived dendritic cells." Therapeutic Advances in Medical Oncology 11 (2019): 1758835919891622.

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