Unit of Medical Oncology and Innovative Therapy and Melanoma Cooperative Group, National Tumor Institute, Naples, Italy.
J Transl Med. 2010 Aug 16;8:76. doi: 10.1186/1479-5876-8-76.
High-dose interferon-alpha 2b (IFN-alpha 2b) is the only approved systemic therapy in the United States for the adjuvant treatment of melanoma. The study objective was to explore the immunomodulatory mechanism of action for IFN-alpha 2b by measuring serum regulatory T cell (Treg), serum transforming growth factor-beta (TGF-beta), interleukin (IL)-10, and autoantibody levels in patients with melanoma treated with the induction phase of the high-dose IFN-alpha 2b regimen.
Patients with melanoma received IFN-alpha 2b administered intravenously (20 MU/m2 each day from day 1 to day 5 for 4 consecutive weeks). Serum Treg levels were measured as whole lymphocytes in CD4+ cells using flow cytometry while TGF-beta, IL-10, and autoantibody levels were measured using enzyme-linked immunosorbent assays.
Twenty-two patients with melanoma received IFN-alpha 2b treatment and were evaluated for Treg levels. Before treatment, Treg levels were significantly higher in patients with melanoma when compared with data from 20 healthy subjects (P = 0.001; Mann-Whitney test). Although a trend for reduction of Treg levels following IFN-α 2b treatment was observed (average decrease 0.29% per week), statistical significance was not achieved. Subgroup analyses indicated higher baseline Treg levels for stage III versus IV disease (P = 0.082), early recurrence versus no recurrence (P = 0.017), deceased versus surviving patients (P = 0.021), and preoperative neoadjuvant versus postoperative adjuvant treatment groups (not significant). No significant effects were observed on the levels of TGF-beta, IL-10, and autoantibodies in patients with melanoma treated with IFN-alpha 2b.
Patients with melanoma in this study showed increased basal levels of Treg that may be relevant to their disease and its progression. Treg levels shifted in patients with melanoma treated with IFN-alpha 2b, although no firm conclusions regarding the role of Tregs as a marker of treatment response or outcome can be made at present.
高剂量干扰素-α 2b（IFN-α 2b）是目前美国唯一批准的用于辅助治疗黑色素瘤的全身性治疗药物。本研究旨在通过测量接受高剂量 IFN-α 2b 诱导期治疗的黑色素瘤患者的血清调节性 T 细胞（Treg）、血清转化生长因子-β（TGF-β）、白细胞介素（IL）-10 和自身抗体水平，探讨 IFN-α 2b 的免疫调节作用机制。
黑色素瘤患者接受 IFN-α 2b 静脉注射治疗（第 1 天至第 5 天每天 20 MU/m2，连续 4 周）。采用流式细胞术检测 CD4+细胞中的全淋巴细胞 Treg 水平，采用酶联免疫吸附试验检测 TGF-β、IL-10 和自身抗体水平。
22 例黑色素瘤患者接受 IFN-α 2b 治疗，并对 Treg 水平进行了评估。治疗前，与 20 例健康对照者相比，黑色素瘤患者的 Treg 水平显著升高（P = 0.001；Mann-Whitney 检验）。尽管观察到 IFN-α 2b 治疗后 Treg 水平呈下降趋势（每周平均下降 0.29%），但未达到统计学意义。亚组分析显示，III 期与 IV 期疾病患者的基线 Treg 水平较高（P = 0.082），早期复发与无复发患者的 Treg 水平较高（P = 0.017），死亡与存活患者的 Treg 水平较高（P = 0.021），术前新辅助与术后辅助治疗组的 Treg 水平较高（无统计学意义）。接受 IFN-α 2b 治疗的黑色素瘤患者的 TGF-β、IL-10 和自身抗体水平无显著变化。
本研究中黑色素瘤患者的 Treg 基础水平升高，这可能与其疾病及其进展有关。接受 IFN-α 2b 治疗的黑色素瘤患者的 Treg 水平发生了变化，但目前尚不能确定 Treg 是否可作为治疗反应或预后的标志物。
