Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma. (2nd November 2019)

• Record Type: Journal Article
• Authors: Blümel, Edda; Willerslev-Olsen, Andreas; Gluud, Maria; Lindahl, Lise M.; Fredholm, Simon; Nastasi, Claudia; Krejsgaard, Thorbjørn; Surewaard, Bas G. J.; Koralov, Sergei B.; Hu, Tengpeng; Persson, Jenny L.; Bonefeld, Charlotte Menné; Geisler, Carsten; Iversen, Lars; Becker, Jürgen C.; Andersen, Mads Hald; Woetmann, Anders; Buus, Terkild Brink; Ødum, Niels
• Is Part Of: Oncoimmunology. Volume 8:Number 11(2019)
• Publication Date: 2019-11-02
• Subjects: Cutaneous T-cell lymphoma -- Staphylococcus aureus -- alpha-toxin -- disintegrin and metalloproteinase domain-containing protein 10; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2019.1641387
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: 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.