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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. Eriksen, Thorbjørn Krejsgaard, Charlotte M. Bonefeld, Carsten Geisler, Tomas Mustelin, Erik Langhoff, Michael Givskov, Anders Woetmann, Mogens Kilian, Thomas Litman, Lars Iversen and Niels Odum

Key Points

  • Antibiotic treatment of CTCL inhibits disease activity and lymphocyte proliferation in lesional skin

  • We provide a novel rationale for aggressive antibiotic treatment as an important adjuvant therapy in patients with advanced stage CTCL

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 eight 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 six out of eight 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 mRNA expression, and cell-signaling pathway analysis indicated that transient aggressive antibiotic therapy was associated with decreased expression of IL-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.

  • Submitted December 1, 2018.
  • Revision received July 19, 2019.
  • Accepted June 16, 2019.