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Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma
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2019 (English)In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 8, no 11, article id e1641387Article in journal (Refereed) Published
Abstract [en]

Staphylococcus aureus is implicated in disease progression in cutaneous T-cell lymphoma (CTCL). Here, we demonstrate that malignant T cell lines derived from CTCL patients as well as primary malignant CD4+ T cells from Sézary syndrome patients are considerably more resistant to alpha-toxin-induced cell death than their non-malignant counterparts. Thus, in a subset of Sézary syndrome patients the ratio between malignant and non-malignant CD4+ T cells increases significantly following exposure to alpha-toxin. Whereas toxin-induced cell death is ADAM10 dependent in healthy CD4+ T cells, resistance to alpha-toxin in malignant T cells involves both downregulation of ADAM10 as well as other resistance mechanisms. In conclusion, we provide first evidence that Staphylococcus aureus derived alpha-toxin can tilt the balance between malignant and non-malignant CD4+ T cells in CTCL patients. Consequently, alpha-toxin may promote disease progression through positive selection of malignant CD4+ T cells, identifying alpha-toxin as a putative drug target in CTCL.

Place, publisher, year, edition, pages
Taylor & Francis, 2019. Vol. 8, no 11, article id e1641387
Keywords [en]
Cutaneous T-cell lymphoma, Staphylococcus aureus, alpha-toxin, disintegrin and metalloproteinase domain-containing protein 10
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-161892DOI: 10.1080/2162402X.2019.1641387ISI: 000476313600001Scopus ID: 2-s2.0-85071108354OAI: oai:DiVA.org:umu-161892DiVA, id: diva2:1341409
Available from: 2019-08-08 Created: 2019-08-08 Last updated: 2020-01-08Bibliographically approved

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Blumel, EddaPersson, Jenny L.
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CiteExportLink to record
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Citation style
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