Staphylococcus aureus enterotoxins induce FOXP3 in neoplastic T cells in Sézary syndrome

Blood Cancer Journal - Tập 10 Số 5
Andreas Willerslev-Olsen1,2, Terkild B. Buus1,2, Claudia Nastasi1,2, Edda Blümel1,2, Maria Gluud1,2, Charlotte M. Bonefeld1,2, Carsten Geisler1,2, Lise M. Lindahl3, Maarten H. Vermeer4, Mariusz A. Wasik5, Lars Iversen3, Jürgen C. Becker6, Mads Hald Andersen7, Lise Mette Rahbek Gjerdrum8, Ivan V. Litvinov9, Thomas Litman1,2, Thorbjørn Krejsgaard1,2, Anders Woetmann1,2, Niels Ødum1,2
1Department of Immunology and Microbiology
2LEO Foundation Skin Immunology Research Center, University of Copenhagen, Copenhagen, Denmark
3Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark
4Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands
5Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA USA
6Department of Translational Skin Cancer Research, German Cancer Consortium (DKTK), University Hospital of Essen, Essen, Germany
7Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark
8Department of Pathology, Zealand University Hospital, Roskilde, Denmark
9Division of Dermatology, McGill University Health Centre, Montreal, QC, Canada

Tóm tắt

AbstractSézary syndrome (SS) is a heterogeneous leukemic subtype of cutaneous T-cell lymphoma (CTCL) with generalized erythroderma, lymphadenopathy, and a poor prognosis. Advanced disease is invariably associated with severe immune dysregulation and the majority of patients die from infectious complications caused by microorganisms such as,Staphylococcus aureus, rather than from the lymphoma per se. Here, we examined if staphylococcal enterotoxins (SE) may shape the phenotype of malignant SS cells, including expression of the regulatory T-cell-associated marker FOXP3. Our studies with primary and cultured malignant cells show that SE induce expression of FOXP3 in malignant cells when exposed to nonmalignant cells. Mutations in the MHC class II binding domain of SE-A (SEA) largely block the effect indicating that the response relies at least in part on the MHC class II-mediated antigen presentation. Transwell experiments show that the effect is induced by soluble factors, partly blocked by anti-IL-2 antibody, and depends on STAT5 activation in malignant cells. Collectively, these findings show that SE stimulate nonmalignant cells to induce FOXP3 expression in malignant cells. Thus, differences in exposure to environmental factors, such as bacterial toxins may explain the heterogeneous FOXP3 expression in malignant cells in SS.

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Blood Cancer Journal

Tập 10 Số 5

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