Oncotarget

Research Papers:

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 and Niels Ødum _

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Oncotarget. 2019; 10:4894-4906. https://doi.org/10.18632/oncotarget.27122

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Abstract

Tengpeng Hu1, Terkild Brink Buus1, Thorbjørn Krejsgaard1, Anneline Nansen2, Betina Kerstin Lundholt2, Pieter Spee3, Simon Fredholm1, David Leander Petersen1, Edda Blümel1, Maria Gluud1, Madalena N. Monteiro1, Andreas Willerslev-Olsen1, Mads Hald Andersen1,4, Per thor Straten1,4, Özcan Met1,4, Veronica Stolearenco1, Hanne Fogh5, Robert Gniadecki5, Claudia Nastasi1, Thomas Litman1, Anders Woetmann1, Lise Mette Rahbek Gjerdrum6 and Niels Ødum1

1 LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark

2 Department of Molecular Pharmacology, Zealand Pharma A/S, Glostrup, Denmark

3 PS Pharmaconsult, Allerød, Denmark

4 Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University Hospital at Herlev, Copenhagen, Denmark

5 Department of Dermatology, Copenhagen University Hospital at Bispebjerg, Copenhagen, Denmark

6 Department of Pathology, Zealand University Hospital, Roskilde, Denmark

Correspondence to:

Niels Ødum,email: ndum@sund.ku.dk

Keywords: Sézary syndrome; Kv1.3 channel; ShK; cutaneous T-cell lymphoma; cancer

Received: March 11, 2019     Accepted: July 15, 2019     Published: August 06, 2019

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.


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