Antibiotics inhibit tumor and disease activity in cutaneous T cell lymphoma

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Lise M Lindahl
  • Andreas Willerslev-Olsen, Institue of International health, Immunology, University of Copenhagen, Denmark.
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  • Lise M R Gjerdrum, Department of Pathology, Zealand University Hospital, Roskilde, Denmark.
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  • Pia R Nielsen, Department of Pathology, Zealand University Hospital, Roskilde, Denmark.
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  • Edda Blümel, 1Copenhagen University Hospital, Copenhagen, Denmark. 2Aarhus University Hospital, Aarhus, Denmark. 3University of Copenhagen, Copenhagen, Denmark. 4Odense University Hospital, Odense, Denmark.
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  • Anne H Rittig
  • Pamela Celis
  • Bjorn Herpers, Regional Public Health Laboratory Kennemerland, Netherlands.
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  • Jürgen C Becker, Translational Skin Cancer Research, German Cancer Consortium (DKTK), Site University Medicine Essen, Germany.
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  • Birgitte Stausbøl-Grøn
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  • Mariusz A Wasik, Pathology, Fox Chase Cancer Center, United States.
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  • Maria Gluud, ISIM, University of Copenhagen, Denmark.
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  • Simon Fredholm, ISIM, University of Copenhagen, Denmark.
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  • Terkild B Buus, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
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  • Claus Johansen
  • Claudia Nastasi, ISIM, University of Copenhagen, Denmark.
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  • Lukas Peiffer, Department of Translational Skin Cancer Research, German Cancer Consortium (DKTK), Dermatology, University Hospital of Essen, Germany.
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  • Linda Kubat, Department of Translational Skin Cancer Research, German Cancer Consortium (DKTK), Dermatology, University Hospital of Essen, Germany.
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  • Michael Bzorek, Department of Pathology, Zealand University Hospital, Roskilde, Denmark.
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  • Jens O Eriksen, b Department of Surgical Pathology , Zealand University Hospital , Slagelse , Denmark.
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  • Thorbjørn Krejsgaard, Centre for Bacterial Stress Response and Persistence, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus, Denmark.
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  • Charlotte M Bonefeld, 1Copenhagen University Hospital, Copenhagen, Denmark. 2Aarhus University Hospital, Aarhus, Denmark. 3University of Copenhagen, Copenhagen, Denmark. 4Odense University Hospital, Odense, Denmark.
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  • Carsten Geisler, Department of Immunolog, University of Copenhagen, Denmark.
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  • Tomas Mustelin, Division of Rheumatology, University of Washington School of Medicine, United States.
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  • Erik Langhoff, James J. Peters VA Medical Center, Veterans Affairs, United States.
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  • Michael Givskov, Costerton Biofilm Center, Institute of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark.
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  • Anders Woetmann, ISIM, University of Copenhagen, Denmark.
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  • Mogens Kilian
  • Thomas Litman, ISIM, University of Copenhagen, Denmark.
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  • Lars Iversen
  • Niels Odum, Int. health, immunology, & microbiology, University of Copenhagen, Denmark ndum@sund.ku.dk.

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.

Original languageEnglish
JournalBlood
Volume134
Issue13
Pages (from-to)1072-1083
Number of pages12
ISSN0006-4971
DOIs
Publication statusPublished - 26 Sep 2019

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