Interleukin (IL)-7 plays a vital role in proliferation and activation of T cells, however, its signaling through CD127 is impaired in T cells in cancers and chronic infections. The mechanisms underlying T helper 17 (Th17) cell responses by IL-7 in melanoma remain not fully understood. The aim of this study was to assess the effect of IL-7 signaling on Th17 responses in patients with primary cutaneous melanoma. Healthy and primary cutaneous melanoma donors were selected for this study of Th17 cell function. IL-17+CD4+ Th17 cells and CD127 expression on Th17 cells were determined by flow cytometry. Cytokine level was measured by ELISA. Peripheral and tissue-infiltrating CD4+ T cells were isolated using magnetic beads, and then stimulated with IL-7 and/or signal transducer and activator of transcription 5 inhibitor. Activated signaling molecules were analyzed by flow cytometry. Peripheral and tumor-infiltrating Th17 cells percentage was decreased, while peripheral IL-7 level was also reduced in melanoma patients. There was no significant difference of CD127 expression on Th17 cells between melanoma patients and controls. Antiapoptotic protein Bcl-2 was downregulated, whereas proapoptotic protein-activated caspase-3 was upregulated in peripheral and tissue-infiltrating Th17 cells in melanoma patients. Higher concentration of IL-7 (10 ng/mL), but not lower IL-7 concentration (1 ng/mL), promoted Bcl-2 expression and decreased caspase-3 expression in Th17 cells in melanoma patients. Inhibition of signal transducer and activator of transcription 5 resulted in the downregulation of Bcl-2 while upregulation of caspase-3 in Th17 cells. The present data suggested that reduced IL-7 responsiveness might be insufficient for Th17 activation in patients with primary cutaneous melanoma.

中文翻译：

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白细胞介素 7 在原发性皮肤黑色素瘤患者中诱导 T 辅助细胞 17 细胞反应。

白细胞介素 (IL)-7 在 T 细胞的增殖和激活中发挥着至关重要的作用，然而，其通过 CD127 的信号传导在癌症和慢性感染的 T 细胞中受到损害。黑色素瘤中 IL-7 辅助 T 辅助细胞 17 (Th17) 细胞反应的机制尚不完全清楚。本研究的目的是评估 IL-7 信号传导对原发性皮肤黑色素瘤患者 Th17 反应的影响。本次 Th17 细胞功能研究选择了健康的原发性皮肤黑色素瘤供体。通过流式细胞术测定IL-17+CD4+Th17细胞和Th17细胞上的CD127表达。通过ELISA测量细胞因子水平。使用磁珠分离外周和组织浸润的 CD4+ T 细胞，然后用 IL-7 和/或信号转导器和转录 5 抑制剂的激活剂刺激。通过流式细胞术分析激活的信号分子。黑色素瘤患者的外周和肿瘤浸润 Th17 细胞百分比下降，而外周 IL-7 水平也降低。黑色素瘤患者和对照组之间 Th17 细胞上 CD127 的表达没有显着差异。在黑色素瘤患者的外周和组织浸润 Th17 细胞中，抗​​凋亡蛋白 Bcl-2 下调，而促凋亡蛋白激活的 caspase-3 上调。在黑色素瘤患者的 Th17 细胞中，较高浓度的 IL-7 (10 ng/mL)，而不是较低的 IL-7 浓度 (1 ng/mL)，会促进 Bcl-2 表达并降低 caspase-3 表达。抑制信号转导子和转录激活子 5 导致 Th17 细胞中 Bcl-2 下调，同时 caspase-3 上调。目前的数据表明，降低的 IL-7 反应性可能不足以激活原发性皮肤黑色素瘤患者的 Th17。