Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma
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Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma. / Blümel, Edda; Willerslev-Olsen, Andreas; Gluud, Maria; Lindahl, Lise Maria; 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.
In: OncoImmunology, Vol. 8, No. 11, e1641387, 2019.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2019
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
VL - 8
JO - OncoImmunology
JF - OncoImmunology
SN - 2162-4011
IS - 11
M1 - e1641387
ER -
ID: 226263012