LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Department of in vivo Pharmacology, Zealand Pharma A/S, Glostrup, Denmark.
Dermatology. 2020;236(2):123-132. doi: 10.1159/000502137. Epub 2019 Sep 19.
The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed by effector memory T cells (TEM) and plays an important role in their activation and proliferation. Mycosis fungoides (MF), the most common subtype of cutaneous T-cell lymphoma (CTCL), was recently proposed to be a malignancy of skin-resident TEM. However, the expression of Kv1.3 in CTCL has not been investigated.
This study aims to examine the expression of Kv1.3 in situ and in vitro in CTCL.
The expression of Kv1.3 was examined by immunohistochemistry in skin lesions from 38 patients with MF, 4 patients with Sézary syndrome (SS), and 27 patients with benign dermatosis. In 4 malignant T-cell lines of CTCL (Myla2059, PB2B, SeAx, and Mac2a) and a non-malignant T-cell line (MyLa1850), the expression of Kv1.3 was determined by flow cytometry. The proliferation of those cell lines treated with various concentrations of Kv1.3 inhibitor ShK was measured by 3H-thymdine incorporation.
Half of the MF patients (19/38) displayed partial Kv1.3 expression including 1 patient with moderate Kv1.3 positivity, while the other half (19/38) exhibited Kv1.3 negativity. An almost identical distribution was observed in patients with benign conditions, that is, 44.4% (12/27) were partially positive for Kv1.3 including 1 patient with moderate Kv1.3 positivity, while 55.6% (15/27) were Kv1.3 negative. In contrast, 3 in 4 SS patients displayed partial Kv1.3 positivity including 2 patients with weak staining and 1 with moderate staining, while 1 in 4 SS patients was Kv1.3 negative. In addition, all malignant T-cell lines, and a non-malignant T-cell line, displayed low Kv1.3 surface expression with a similar pattern. Whereas 2 cell lines (PB2B and Mac2a) were sensitive to Kv1.3 blockade, the other 2 (Myla2059 and SeAx) were completely resistant.
We provide the first evidence of a heterogeneous Kv1.3 expression in situ in CTCL lesions.
电压门控钾通道 Kv1.3（KCNA3）由效应记忆 T 细胞（TEM）表达，在其激活和增殖中发挥重要作用。蕈样肉芽肿（MF）是皮肤 T 细胞淋巴瘤（CTCL）最常见的亚型，最近被认为是皮肤驻留 TEM 的恶性肿瘤。然而，CTCL 中 Kv1.3 的表达尚未被研究。
本研究旨在检测 CTCL 中 Kv1.3 的原位和体外表达。
通过免疫组化检测 38 例 MF 患者、4 例 SS 患者和 27 例良性皮肤病患者皮肤病变中 Kv1.3 的表达。在 4 种 CTCL 的恶性 T 细胞系（Myla2059、PB2B、SeAx 和 Mac2a）和一种非恶性 T 细胞系（MyLa1850）中，通过流式细胞术测定 Kv1.3 的表达。通过 3H-胸腺嘧啶掺入测量用不同浓度 Kv1.3 抑制剂 ShK 处理的那些细胞系的增殖。
一半的 MF 患者（19/38）显示部分 Kv1.3 表达，包括 1 例中度 Kv1.3 阳性患者，而另一半（19/38）显示 Kv1.3 阴性。良性疾病患者也观察到几乎相同的分布，即 44.4%（12/27）对 Kv1.3 呈部分阳性，包括 1 例中度 Kv1.3 阳性患者，而 55.6%（15/27）为 Kv1.3 阴性。相比之下，4 例 SS 患者中的 3 例显示部分 Kv1.3 阳性，包括 2 例弱阳性和 1 例中度阳性，而 4 例 SS 患者中的 1 例为 Kv1.3 阴性。此外，所有恶性 T 细胞系和一种非恶性 T 细胞系均显示出低水平的 Kv1.3 表面表达，模式相似。虽然 2 个细胞系（PB2B 和 Mac2a）对 Kv1.3 阻断敏感，但另外 2 个（Myla2059 和 SeAx）则完全耐药。
我们提供了 CTCL 病变中 Kv1.3 表达异质性的首个证据。
