聚乙二醇化重组人粒细胞集落刺激因子调节小细胞肺癌患者的免疫状态。
Pegylated recombinant human granulocyte colony-stimulating factor regulates the immune status of patients with small cell lung cancer.
机构信息
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Research and Development, Geneplus-Beijing, Beijing, China.
出版信息
Thorac Cancer. 2020 Mar;11(3):713-722. doi: 10.1111/1759-7714.13322. Epub 2020 Feb 5.
BACKGROUND
Small cell lung cancer (SCLC) is an aggressive disease involving immunodeficiency for which chemotherapy is the standard treatment. Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) is widely used for primary or secondary prophylaxis of febrile neutropenia (FN) in chemotherapy. However, whether PEG-rhG-CSF influences immune cells, such as lymphocytes, remains unclear.
METHODS
A total of 17 treatment-naïve SCLC patients were prospectively enrolled and divided into the PEG-rhG-CSF and control groups according to their FN risk. Longitudinal sampling of peripheral blood was performed before, after and 4-6 days after the first cycle of chemotherapy. Flow cytometry was used to assess lymphocyte subsets, including CD3 T, CD4 T, CD8 T, NK, and B cells. The diversity and clonality of the T-cell receptor (TCR) repertoire was analyzed by next-generation sequencing.
RESULTS
In the PEG-rhG-CSF group, the proportions of CD3 T and CD4 T cells had increased significantly (P = 0.002, P = 0.020, respectively), whereas there was no increase in CD8 T cells. Further, TCR diversity increased (P = 0.009) and clonality decreased (P = 0.004) significantly after PEG-rhG-CSF treatment. However, these factors showed opposite trends before and after chemotherapy. Vβ and Jβ gene fragment types, which determine TCR diversity, were significantly amplified in the PEG-rhG-CSF group. The change in TCR diversity was significantly correlated with changes in the CD3 T or CD4 T cell proportions, but not the CD8 T cell proportion.
CONCLUSIONS
PEG-rhG-CSF regulates the immune status of SCLC patients; CD4 T cells may be the main effector cells involved in this process. These findings may optimize the treatment of SCLC.
KEY POINTS
PEG-rhG-CSF regulates SCLC immunity. PEG-rhG-CSF increased CD3 T and CD4 T cell proportions. PEG-rhG-CSF increased TCR diversity and decreased clonality in peripheral blood. Change in TCR diversity were correlated with CD3 T or CD4 T changes.
背景
小细胞肺癌（SCLC）是一种免疫缺陷相关的侵袭性疾病，化疗是其标准治疗方法。聚乙二醇化重组人粒细胞集落刺激因子（PEG-rhG-CSF）广泛用于预防化疗引起的发热性中性粒细胞减少症（FN）的一级或二级预防。然而，PEG-rhG-CSF 是否会影响淋巴细胞等免疫细胞尚不清楚。
方法
前瞻性纳入 17 例初治 SCLC 患者，根据 FN 风险分为 PEG-rhG-CSF 组和对照组。在化疗第 1 周期前、后和第 4-6 天进行外周血纵向采样。采用流式细胞术检测 CD3 T、CD4 T、CD8 T、NK 和 B 细胞等淋巴细胞亚群。采用下一代测序分析 T 细胞受体（TCR）库的多样性和克隆性。
结果
PEG-rhG-CSF 组 CD3 T 和 CD4 T 细胞比例明显增加（P = 0.002，P = 0.020），而 CD8 T 细胞无增加。此外，PEG-rhG-CSF 治疗后 TCR 多样性增加（P = 0.009），克隆性降低（P = 0.004）。但化疗前后这些因素呈相反趋势。决定 TCR 多样性的 Vβ 和 Jβ 基因片段类型在 PEG-rhG-CSF 组中明显扩增。TCR 多样性的变化与 CD3 T 或 CD4 T 细胞比例的变化显著相关，而与 CD8 T 细胞比例无关。
结论
PEG-rhG-CSF 调节 SCLC 患者的免疫状态；CD4 T 细胞可能是参与该过程的主要效应细胞。这些发现可能优化 SCLC 的治疗。
重点
PEG-rhG-CSF 调节 SCLC 免疫。PEG-rhG-CSF 增加 CD3 T 和 CD4 T 细胞比例。PEG-rhG-CSF 增加外周血 TCR 多样性并降低克隆性。TCR 多样性的变化与 CD3 T 或 CD4 T 的变化相关。
Zotero 插件