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

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.

SUBMITTER: Lindahl LM

PROVIDER: S-EPMC6764271 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Lindahl Lise M LM Willerslev-Olsen Andreas A Gjerdrum Lise M R LMR Nielsen Pia R PR Blümel Edda E Rittig Anne H AH Celis Pamela P Herpers Bjorn B Becker Jürgen C JC Stausbøl-Grøn Birgitte B Wasik Mariusz A MA Gluud Maria M Fredholm Simon S Buus Terkild B TB Johansen Claus C Nastasi Claudia C Peiffer Lukas L Kubat Linda L Bzorek Michael M Eriksen Jens O JO Krejsgaard Thorbjørn T Bonefeld Charlotte M CM Geisler Carsten C Mustelin Tomas T Langhoff Erik E Givskov Michael M Woetmann Anders A Kilian Mogens M Litman Thomas T Iversen Lars L Odum Niels N

Blood 20190722 13

It has been proposed that CD4 T-cell responses to <i>Staphylococcus aureus</i> (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, ...[more]

PMID: 31331920

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Project description:Lessons learnedStaphylococcus aureus infection in cutaneous T-cell lymphoma (CTCL) is thought to contribute to disease progression; thus, adjunctive treatment with antibiotics warrants further investigation. This trial of antibiotic therapy followed by imiquimod in early stage CTCL was not completed because of difficulties with patient accrual.BackgroundCutaneous T-cell lymphoma (CTCL), a form of non-Hodgkin lymphoma, is a heterogeneous group of malignancies of mature memory T lymphocytes. It has an annual age-adjusted incidence of 7.5 per million persons in the U.S. population [1]. The etiology of CTCL is unknown, but epidemiological studies have reported potential associations with environmental and occupational factors, including Agent Orange exposure in Vietnam Veterans [2]. Both topical and systemic therapies have been identified as effective in CTCL; the choice of treatment is dependent on disease stage, with the overall goal of improving symptoms given the chronic and recurrent nature of the disease. Several studies have suggested that CTCL is exacerbated by the presence of Staphylococcus aureus in the skin and can be ameliorated by treatment with antibiotics [3].MethodsOur study was designed to assess the effects of antibiotics and imiquimod on early stage CTCL. Patients between the ages of 30-89 years with stage I and II CTCL were eligible for enrollment. They could not be receiving concurrent therapy, and the study design included a 14-day washout period after discontinuation of CTCL therapy. The washout period was followed by doxycycline 100 mg p.o. b.i.d. for 14 days and then two packets (250 mg per packet) of imiquimod 5% cream topically to the most clinically active lesions 3 days a week (Monday, Wednesday, and Friday) for 28 days. Skin lesions were measured using the modified Severity Weighted Assessment Tool (mSWAT).ResultsOur study enrolled only two patients with early stage CTCL because of difficulty locating patients with active CTCL able to discontinue all therapy. The two enrolled patients completed all therapy. One patient had a complete response after imiquimod, whereas the other patient had stable disease.ConclusionAntibiotics and imiquimod have reported activity as single agents in CTCL; we did not enroll enough patients to assess value in the sequence of antibiotic therapy followed by imiquimod.

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

Publications

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

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