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Blood. 2019 Jul 22. pii: blood.2018888107. doi: 10.1182/blood.2018888107. [Epub ahead of print]

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

Author information

1
Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark, Denmark.
2
Institue of International health, Immunology, University of Copenhagen, Denmark.
3
Pathology, Zealand University Hospital, Denmark.
4
Department of Pathology, Zealand University Hospital, Denmark.
5
University of Copenhagen, Denmark.
6
Department of Dermatology, Aarhus University, Denmark.
7
Department of Molecular Medicine / MOMA, Aarhus university hospital, Denmark.
8
Regional Public Health Laboratory Kennemerland, Netherlands.
9
Translational Skin Cancer Research, German Cancer Consortium (DKTK), Site University Medicine Essen, Germany.
10
Department of Dermatology, Aarhus University Hospital.
11
Pathology, Fox Chase Cancer Center, United States.
12
ISIM, University of Copenhagen, Denmark.
13
Department of Immunology and Microbiology, University of Copenhagen, Denmark.
14
Department of Translational Skin Cancer Research, German Cancer Consortium (DKTK), Dermatology, University Hospital of Essen, Germany.
15
Department of Surgical Pathology, Zealand University Hospital, Denmark.
16
Department of Molecular Biology, University of Copenhagen, Denmark.
17
Department of Immunolog, University of Copenhagen, Denmark.
18
Division of Rheumatology, University of Washington School of Medicine, United States.
19
James J. Peters VA Medical Center, Veterans Affairs, United States.
20
Costerton Biofilm Center, University of Copenhagen, Denmark.
21
Department of Biomedicine, Aarhus University, Denmark.
22
Department of Dermatology, Aarhus University Hospital, Denmark.
23
Int. health, immunology, & microbiology, University of Copenhagen, Denmark ndum@sund.ku.dk.

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.

PMID:
31331920
DOI:
10.1182/blood.2018888107

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