Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome

Tengpeng Hu; Terkild Brink Buus; Thorbjørn Krejsgaard; Anneline Nansen; Betina Kerstin Lundholt; Pieter Spee; Simon Fredholm; David Leander Petersen; Edda Blümel; Maria Gluud; Madalena N Monteiro; Andreas Willerslev-Olsen; Mads Hald Andersen; Per Thor Straten; Özcan Met; Veronica Stolearenco; Hanne Fogh; Robert Gniadecki; Claudia Nastasi; Thomas Litman; Anders Woetmann; Lise Mette Rahbek Gjerdrum; Niels Ødum

doi:10.18632/oncotarget.27122

Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome

Tengpeng Hu, Terkild Brink Buus, Thorbjørn Krejsgaard, Anneline Nansen, Betina Kerstin Lundholt, Pieter Spee, Simon Fredholm, David Leander Petersen, Edda Blümel, Maria Gluud, Madalena N Monteiro, Andreas Willerslev-Olsen, Mads Hald Andersen, Per Thor Straten, Özcan Met, Veronica Stolearenco, Hanne Fogh, Robert Gniadecki, Claudia Nastasi, Thomas LitmanAnders Woetmann, Lise Mette Rahbek Gjerdrum, Niels Ødum

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Abstract

The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed by a subset of chronically activated memory T cells and plays an important role in their activation and proliferation. Here, we show that primary malignant T cells isolated from patients with Sézary syndrome (SS) express Kv1.3 and are sensitive to potent Kv1.3 inhibitors ShK and Vm24, but not sensitive to a less potent inhibitor [N17A/F32T]-AnTx. Kv1.3 blockade inhibits CD3/CD28-induced proliferation and IL-9 expression by SS cells in a concentration-dependent manner. In parallel, CD3/CD28-mediated CD25 induction is inhibited, whereas Kv1.3 blockade has no effect on apoptosis or cell death as judged by Annexin V and PI staining. In conclusion, we provide the first evidence that malignant T cells in SS express functional Kv1.3 channels and that Kv1.3 blockade inhibits activation-induced proliferation as well as cytokine and cytokine receptor expression in malignant T cells, suggesting that Kv1.3 is a potential target for therapy in SS.

Original language	English
Journal	OncoTarget
Volume	10
Issue number	47
Pages (from-to)	4894-4906
Number of pages	13
ISSN	1949-2553
DOIs	https://doi.org/10.18632/oncotarget.27122
Publication status	Published - 1 Aug 2019

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Hu, T., Buus, T. B., Krejsgaard, T., Nansen, A., Lundholt, B. K., Spee, P., Fredholm, S., Petersen, D. L., Blümel, E., Gluud, M., Monteiro, M. N., Willerslev-Olsen, A., Andersen, M. H., Straten, P. T., Met, Ö., Stolearenco, V., Fogh, H., Gniadecki, R., Nastasi, C., ... Ødum, N. (2019). Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome. OncoTarget, 10(47), 4894-4906. https://doi.org/10.18632/oncotarget.27122

Hu, T, Buus, TB, Krejsgaard, T, Nansen, A, Lundholt, BK, Spee, P, Fredholm, S, Petersen, DL, Blümel, E, Gluud, M, Monteiro, MN, Willerslev-Olsen, A, Andersen, MH , Straten, PT , Met, Ö, Stolearenco, V, Fogh, H, Gniadecki, R, Nastasi, C, Litman, T, Woetmann, A, Gjerdrum, LMR & Ødum, N 2019, 'Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome', OncoTarget, vol. 10, no. 47, pp. 4894-4906. https://doi.org/10.18632/oncotarget.27122

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title = "Expression and function of Kv1.3 channel in malignant T cells in S{\'e}zary syndrome",

abstract = "The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed by a subset of chronically activated memory T cells and plays an important role in their activation and proliferation. Here, we show that primary malignant T cells isolated from patients with S{\'e}zary syndrome (SS) express Kv1.3 and are sensitive to potent Kv1.3 inhibitors ShK and Vm24, but not sensitive to a less potent inhibitor [N17A/F32T]-AnTx. Kv1.3 blockade inhibits CD3/CD28-induced proliferation and IL-9 expression by SS cells in a concentration-dependent manner. In parallel, CD3/CD28-mediated CD25 induction is inhibited, whereas Kv1.3 blockade has no effect on apoptosis or cell death as judged by Annexin V and PI staining. In conclusion, we provide the first evidence that malignant T cells in SS express functional Kv1.3 channels and that Kv1.3 blockade inhibits activation-induced proliferation as well as cytokine and cytokine receptor expression in malignant T cells, suggesting that Kv1.3 is a potential target for therapy in SS.",

author = "Tengpeng Hu and Buus, {Terkild Brink} and Thorbj{\o}rn Krejsgaard and Anneline Nansen and Lundholt, {Betina Kerstin} and Pieter Spee and Simon Fredholm and Petersen, {David Leander} and Edda Bl{\"u}mel and Maria Gluud and Monteiro, {Madalena N} and Andreas Willerslev-Olsen and Andersen, {Mads Hald} and Straten, {Per Thor} and {\"O}zcan Met and Veronica Stolearenco and Hanne Fogh and Robert Gniadecki and Claudia Nastasi and Thomas Litman and Anders Woetmann and Gjerdrum, {Lise Mette Rahbek} and Niels {\O}dum",

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T1 - Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome

AU - Hu, Tengpeng

AU - Buus, Terkild Brink

AU - Krejsgaard, Thorbjørn

AU - Nansen, Anneline

AU - Lundholt, Betina Kerstin

AU - Spee, Pieter

AU - Fredholm, Simon

AU - Petersen, David Leander

AU - Blümel, Edda

AU - Gluud, Maria

AU - Monteiro, Madalena N

AU - Willerslev-Olsen, Andreas

AU - Andersen, Mads Hald

AU - Straten, Per Thor

AU - Met, Özcan

AU - Stolearenco, Veronica

AU - Fogh, Hanne

AU - Gniadecki, Robert

AU - Nastasi, Claudia

AU - Litman, Thomas

AU - Woetmann, Anders

AU - Gjerdrum, Lise Mette Rahbek

AU - Ødum, Niels

PY - 2019/8/1

Y1 - 2019/8/1

N2 - The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed by a subset of chronically activated memory T cells and plays an important role in their activation and proliferation. Here, we show that primary malignant T cells isolated from patients with Sézary syndrome (SS) express Kv1.3 and are sensitive to potent Kv1.3 inhibitors ShK and Vm24, but not sensitive to a less potent inhibitor [N17A/F32T]-AnTx. Kv1.3 blockade inhibits CD3/CD28-induced proliferation and IL-9 expression by SS cells in a concentration-dependent manner. In parallel, CD3/CD28-mediated CD25 induction is inhibited, whereas Kv1.3 blockade has no effect on apoptosis or cell death as judged by Annexin V and PI staining. In conclusion, we provide the first evidence that malignant T cells in SS express functional Kv1.3 channels and that Kv1.3 blockade inhibits activation-induced proliferation as well as cytokine and cytokine receptor expression in malignant T cells, suggesting that Kv1.3 is a potential target for therapy in SS.

AB - The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed by a subset of chronically activated memory T cells and plays an important role in their activation and proliferation. Here, we show that primary malignant T cells isolated from patients with Sézary syndrome (SS) express Kv1.3 and are sensitive to potent Kv1.3 inhibitors ShK and Vm24, but not sensitive to a less potent inhibitor [N17A/F32T]-AnTx. Kv1.3 blockade inhibits CD3/CD28-induced proliferation and IL-9 expression by SS cells in a concentration-dependent manner. In parallel, CD3/CD28-mediated CD25 induction is inhibited, whereas Kv1.3 blockade has no effect on apoptosis or cell death as judged by Annexin V and PI staining. In conclusion, we provide the first evidence that malignant T cells in SS express functional Kv1.3 channels and that Kv1.3 blockade inhibits activation-induced proliferation as well as cytokine and cytokine receptor expression in malignant T cells, suggesting that Kv1.3 is a potential target for therapy in SS.

U2 - 10.18632/oncotarget.27122

DO - 10.18632/oncotarget.27122

M3 - Journal article

C2 - 31448055

SN - 1949-2553

VL - 10

SP - 4894

EP - 4906

JO - OncoTarget

JF - OncoTarget

IS - 47

ER -

Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome

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