[Clinical significance of T lymphocyte subset changes after first line chemotherapy in peripheral blood from patients with advanced stage adenocarcinoma cell lung cancer]

Zhongguo Fei Ai Za Zhi. 2012 Mar;15(3):164-71. doi: 10.3779/j.issn.1009-3419.2012.03.06.
[Article in Chinese]

Abstract

Background and objective: The immune function disorder relates closely to the occurrence, metastasis, and prognosis of cancer. T lymphocyte subsets take an important role in immune function. We identified the dynamic changes of the immune system by investigating the levels of T lymphocyte subsets in peripheral blood of lung cancer patients with advanced stage adenocarcinoma undergoing first line chemotherapy. The results aided the search for rational chemo-immunotherapy strategies in lung cancer treatment.

Methods: Samples from 49 patients with pathologically demonstrated advanced stage adenocarcinoma cell lung cancer were compared with those from 33 healthy donors. Subsequently, the patients were separately treated with Docetaxol-based or Pemetrexed-based therapy. Peripheral blood samples at different time points after therapy were analyzed by flowcytometry. The lymphocyte subsets of the total lymphocytes were compared. Independent sample t test was used for the quantitative data analysis.

Results: The percentage of CD3+, CD3+CD4+, CD4+CD25+ cells of the lung cancer patients significantly varied from those of the healthy donors, the P values are 0.012, 0.034 and 0.006 separately. The CD3+ and CD3+CD4+ levels increased significantly on the 4th and 7th-10th day post-chemotherapy, which return to normal levels on the 21th day. The CD3+ level increased significantly both in the treatment group on all time points, while the CD3+, CD3+CD4+, CD4+/CD8+ levels significantly increased and the CD3+CD8+, CD8+CD28- levels significantly decreased on the 4th day in Pemetrexed group. The CD3+CD4+ levels increased significantly on the 4th and 7th-10th day and the CD3+CD8+, CD8+CD28- levels decreased on the 4th day in partial response group.

Conclusions: The immune function of advanced stage adenocarcinoma cell lung cancer patients was evidently suppressed, and was restored at the 4th day, followed by a reduction at the 21st day after chemotherapy. On the 4th day, Pemetrexed showed better effect on the immune system. The change of immune system post-chemotherapy could be related with the prognosis.

背景与目的: 机体的免疫功能异常与恶性肿瘤的发生、发展、转移及预后密切相关。T淋巴细胞亚群是反映细胞免疫功能的重要指标之一。本实验研究晚期肺腺癌患者一线化疗后外周血T淋巴细胞数量的动态变化,探讨化疗后机体免疫状态变化的动态过程,为制定化疗联合免疫治疗方案提供实验依据。

方法: 49例经病理学确诊的Ⅲb期-Ⅳ期肺腺癌患者,与33例正常人比较外周血T淋巴细胞数量。然后患者随机进入2个实验组,分别采用培美曲塞、顺铂联合方案及多西他赛、顺铂联合方案化疗,应用流式细胞仪检测化疗前后不同时间点淋巴细胞的组成。

结果: 肺癌患者的CD3+、CD3+CD4+、CD4+CD25+等T细胞的数量与健康对照组比较存在差异,P值分别为0.012,0.034和0.006;化疗后第4天及第7-10天CD3+、CD3+CD4+比例升高,至第21天逐渐恢复至治疗前水平;2个化疗组比较CD3+细胞比例均升高,而培美曲塞组第4天CD3+、CD3+CD4+、CD4+/CD8+升高,CD3+CD8+及CD8+CD28-比例降低,差异均具有统计学意义。部分缓解患者较早期疾病进展患者的第4天及第7-10天CD3+CD4+细胞升高;第4天CD3+CD8+、CD8+CD28-细胞降低。

结论: 晚期肺腺癌患者免疫功能处于抑制状态。化疗后第4天免疫功能得到一定程度恢复,至第21天恢复至治疗前水平。培美曲塞似乎对化疗后短期内免疫功能的改善有更明显的作用。化疗后免疫格局的改变可能与预后有关。

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / immunology
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Docetaxel
  • Female
  • Flow Cytometry
  • Glutamates / therapeutic use
  • Guanine / analogs & derivatives
  • Guanine / therapeutic use
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Pemetrexed
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / pathology
  • Taxoids / therapeutic use
  • Young Adult

Substances

  • Antineoplastic Agents
  • Glutamates
  • Taxoids
  • Pemetrexed
  • Docetaxel
  • Guanine

Grants and funding

本研究受国家科技部课题项目基金(No.2009BAI86B05)资助