Antibiotics inhibit tumor and disease activity in cutaneous T-cell lymphoma

Lise M. Lindahl, Andreas Willerslev-Olsen, Lise M.R. Gjerdrum, Pia R. Nielsen, Edda Blümel, Anne H. Rittig, Pamela Celis, Bjorn Herpers, Jürgen C. Becker, Birgitte Stausbøl-Grøn, Mariusz A. Wasik, Maria Gluud, Simon Fredholm, Terkild B. Buus, Claus Johansen, Claudia Nastasi, Lukas Peiffer, Linda Kubat, Michael Bzorek, Jens O. EriksenThorbjørn Krejsgaard, Charlotte M. Bonefeld, Carsten Geisler, Tomas Mustelin, Erik Langhoff, Michael Givskov, Anders Woetmann, Mogens Kilian, Thomas Litman, Lars Iversen, Niels Odum

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

It has been proposed that CD4 T-cell responses to Staphylococcus aureus (SA) can inadvertently enhance neoplastic progression in models of skin cancer and cutaneous T-cell lymphoma (CTCL). In this prospective study, we explored the effect of transient antibiotic treatment on tumor cells and disease activity in 8 patients with advanced-stage CTCL. All patients experienced significant decrease in clinical symptoms in response to aggressive, transient antibiotic treatment. In some patients, clinical improvements lasted for more than 8 months. In 6 of 8 patients, a malignant T-cell clone could be identified in lesional skin, and a significant decrease in the fraction of malignant T cells was observed following antibiotics but an otherwise unchanged treatment regimen. Immunohistochemistry, global messenger RNA expression, and cell-signaling pathway analysis indicated that transient aggressive antibiotic therapy was associated with decreased expression of interleukin-2 high-affinity receptors (CD25), STAT3 signaling, and cell proliferation in lesional skin. In conclusion, this study provides novel evidence suggesting that aggressive antibiotic treatment inhibits malignant T cells in lesional skin. Thus, we provide a novel rationale for treatment of SA in advanced CTCL.

Original languageEnglish
Pages (from-to)1072-1083
Number of pages12
JournalBlood
Volume134
Issue number13
DOIs
StatePublished - Sep 26 2019

Keywords

  • Aged
  • Anti-Bacterial Agents/therapeutic use
  • Cell Proliferation/drug effects
  • Female
  • Humans
  • Lymphoma, T-Cell, Cutaneous/drug therapy
  • Male
  • Middle Aged
  • Prospective Studies
  • STAT3 Transcription Factor/metabolism
  • Signal Transduction/drug effects
  • Skin Neoplasms/drug therapy
  • T-Lymphocytes/drug effects

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