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The chemotherapeutic agent topotecan differentially modulates the phenotype and function of dendritic cells

Cancer Immunology, Immunotherapy volume 62, pages 1315–1326 (2013)Cite this article

Abstract

The camptothecin analogue topotecan (TPT) induces tumor cell apoptosis due to interference with topoisomerase I and is clinically used as a second-line chemotherapeutic in the treatment for metastasizing ovarian and small cell lung carcinoma. Based on the more recent finding of TPT-mediated inhibition of the transcription factor hypoxia-induced factor-1α, a hallmark of solid tumors, TPT, is currently tested in clinical trials for its suitability as a first-line chemotherapeutic for the treatment for various types of tumors. Due to the gained clinical interest in TPT and in light of its modulatory effect on signaling pathways, which are also of importance for immune cell functions, we asked for potential effects of TPT on dendritic cells (DCs), the main antigen-presenting cell population of the immune system. Here, we show that TPT at a therapeutically relevant dose partially activated monocyte-derived DCs as reflected by enhanced migratory activity, elevated expression of HLA-DR and costimulatory/maturation markers, and accordingly an increased allogenic CD4+ T cell stimulation. In marked contrast, TPT prevented full maturation of DCs stimulated with a cocktail of proinflammatory mediators, accompanied by somewhat lower upregulation of NF-κB factors p65 and RelB.

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Acknowledgments

The authors thank Claudia Eider and Dirk Prawitt (both Center for Pediatrics and Adolescent Medicine, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany) for providing the cell line IGROV1. We also thank Nicole Voltz (Department of Dermatology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany) for her technical assistance. This work was supported by a grant of the University Medical Center Mainz (MAIFOR) and by the Deutsche Forschungsgemeinschaft (RE 617/1-1 and BA 3505/1-1).

Conflict of interest

The authors have no financial conflicts of interests.

Author information

Affiliations

  1. Department of Dermatology, Clinical Research Unit Allergology, Medical Center of the Johannes Gutenberg-University, Obere Zahlbacher-Str. 63, 55131, Mainz, Germany

    Stefanie Trojandt, Diana Knies, Stefanie Pektor, Stephan Grabbe, Angelika B. Reske-Kunz & Matthias Bros

  2. Max-Planck-Institute for Polymer Research, Physical Chemistry of Polymers, Mainz, Germany

    Sandra Ritz & Volker Mailänder

Authors
  1. Stefanie Trojandt
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  2. Diana Knies
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  3. Stefanie Pektor
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  4. Sandra Ritz
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  5. Volker Mailänder
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  6. Stephan Grabbe
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  7. Angelika B. Reske-Kunz
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  8. Matthias Bros
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Corresponding author

Correspondence to Stefanie Trojandt.

Additional information

Angelika B. Reske-Kunz and Matthias Bros have contributed equally to this study.

Stefanie Trojandt submitted this article in partial fulfillment of the requirements of the doctoral thesis.

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Trojandt, S., Knies, D., Pektor, S. et al. The chemotherapeutic agent topotecan differentially modulates the phenotype and function of dendritic cells. Cancer Immunol Immunother 62, 1315–1326 (2013). https://doi.org/10.1007/s00262-013-1431-9

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  • DOI: https://doi.org/10.1007/s00262-013-1431-9

Keywords

  • Dendritic cell
  • Topotecan
  • Fascin
  • NF-κB
  • AKT