Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4 + T cells in cutaneous T-cell lymphoma

• Published in: Oncoimmunology Vol. 8; no. 11; p. e1641387
• Main 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
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 02.11.2019; Taylor & Francis Group
• Subjects: alpha-toxin; Brief Report; Cutaneous T-cell lymphoma; disintegrin and metalloproteinase domain-containing protein 10; Staphylococcus aureus; alpha-toxin; disintegrin and metalloproteinase domain-containing protein 10; Staphylococcus aureus; Cutaneous T-cell lymphoma
• ISSN: 2162-402X; 2162-4011; 2162-402X
• DOI: 10.1080/2162402X.2019.1641387

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 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.