Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome
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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
Keywords: Sézary syndrome; Kv1.3 channel; ShK; cutaneous T-cell lymphoma; cancer
Received: March 11, 2019 Accepted: July 15, 2019 Published: August 06, 2019
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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