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

TY - JOUR

T1 - Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma

AU - Blümel, Edda

AU - Willerslev-Olsen, Andreas

AU - Gluud, Maria

AU - Lindahl, Lise Maria

AU - Fredholm, Simon

AU - Nastasi, Claudia

AU - Krejsgaard, Thorbjørn

AU - Surewaard, Bas G. J.

AU - Koralov, Sergei B.

AU - Hu, Tengpeng

AU - Persson, Jenny L.

AU - Bonefeld, Charlotte Menné

AU - Geisler, Carsten

AU - Iversen, Lars

AU - Becker, Jürgen C.

AU - Andersen, Mads Hald

AU - Woetmann, Anders

AU - Buus, Terkild Brink

AU - Ødum, Niels

PY - 2019/11/2

Y1 - 2019/11/2

N2 - 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.

AB - 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.

U2 - 10.1080/2162402X.2019.1641387

DO - 10.1080/2162402X.2019.1641387

M3 - Journal article

C2 - 31646088

SN - 2162-4011

VL - 8

JO - OncoImmunology

JF - OncoImmunology

IS - 11

M1 - e1641387

ER -