Mild hyperthermia enhances human monocyte-derived dendritic cell functions and offers potential for applications in vaccination strategies

Knippertz I, Stein MF, Dörrie J, Schaft N, Mueller I, Deinzer A, Steinkasserer A, Nettelbeck DM (2011)

Publication Type: Journal article

Publication year: 2011

Journal

International Journal of Hyperthermia Informa Healthcare

Book Volume: 27

Pages Range: 591-603

Journal Issue: 6

DOI: 10.3109/02656736.2011.589234

Abstract

Dendritic cell (DC)-based immunotherapy has been shown to be a promising strategy for anti-cancer therapy. Nevertheless, only a low overall clinical response rate has been observed in vaccinated patients with advanced cancer and therefore methods to improve DC immuno-stimulatory functions are currently under intense investigation. In this respect, we exposed human monocyte-derived DCs to a physiological temperature stress of 40°C for up to 24 h followed by analysis for (i) expression of different heat shock proteins, (ii) survival, (iii) cell surface maturation markers, (iv) cytokine secretion, and (v) migratory capacity. Furthermore, we examined the ability of heat-shocked DCs to prime nave CD8 + T cells after loading with MelanA peptide, by transfection with MelanA RNA, or by transduction with MelanA by an adenovirus vector. The results clearly indicate that in comparison to control DCs, which remained at 37°C, heat-treated cells revealed no differences concerning the survival rate or their migratory capacity. However, DCs exposed to thermal stress showed a time-dependent enhanced expression of the immune-chaperone heat shock protein 70A and both an up-regulation of co-stimulatory molecules such as CD80, CD83, and CD86 and of the inflammatory cytokine TNF-α. Moreover, these cells had a markedly improved capacity to prime autologous nave CD8 + T cells in vitro in an antigen-specific manner, independent of the method of antigen-loading. Thus, our strategy of heat treatment of DCs offers a promising means to improve DC functions during immune activation which, as a physical method, facilitates straight-forward applications in clinical DC vaccination protocols. © 2011 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

Authors with CRIS profile

Ilka Knippertz Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Jan Dörrie Department of Dermatology Niels Schaft Department of Dermatology Anja Deinzer Institute of General Practice Alexander Steinkasserer Professur für Experimentelle Dermatologie

Involved external institutions

Universitätsklinikum Heidelberg DE Germany (DE)

How to cite

APA:

Knippertz, I., Stein, M.F., Dörrie, J., Schaft, N., Mueller, I., Deinzer, A.,... Nettelbeck, D.M. (2011). Mild hyperthermia enhances human monocyte-derived dendritic cell functions and offers potential for applications in vaccination strategies. International Journal of Hyperthermia, 27(6), 591-603. https://doi.org/10.3109/02656736.2011.589234

MLA:

Knippertz, Ilka, et al. "Mild hyperthermia enhances human monocyte-derived dendritic cell functions and offers potential for applications in vaccination strategies." International Journal of Hyperthermia 27.6 (2011): 591-603.

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