肺癌患者化疗前后T细胞抑制性分子的研究

许钰杰; 张毅; 邝先奎; 段秀芳; 李洁瑶; 李建斌; 张震; 张斌; 王丽萍

doi:10.3969/j.issn.1000-8179.20130292

肺癌患者化疗前后T细胞抑制性分子的研究

Inhibitory molecules expressed in T lymphocytes in patients with lung cancer before and after chemotherapy

摘要

摘要:
目的研究晚期肺癌患者化疗5个周期T淋巴细胞表面抑制性分子（TIM3、PD-1、CTLA-4）的变化。
方法应用流式细胞仪技术检测33例初治晚期肺癌患者化疗5个周期T淋巴细胞表面抑制性分子的表达变化。并与23例健康志愿者作对比。
结果化疗前晚期肺癌患者外周血T淋巴细胞表面抑制性分子的表达明显高于健康对照组, 差异具有统计学意义（P < 0.05）。化疗后19例临床疗效评价为PR或SD的患者, 其外周血CD4⁺TIM3⁺T淋巴细胞、CD8⁺TIM3⁺T淋巴细胞、CD4⁺PD-1⁺T淋巴细胞、CD8⁺PD-1⁺ T淋巴细胞比例在化疗5个周期中降低, 差异有统计学意义（P < 0.05）; 而CD4⁺CTLA-4⁺T淋巴细胞、CD8⁺CTLA-4⁺T淋巴细胞比例呈现下降趋势, 与化疗前相比无显著性差异（P>0.05）。
结论晚期肺癌患者的免疫功能处于抑制状态。有效的化疗可降低T淋巴细胞表面抑制性分子表达, 改善肿瘤对免疫功能的抑制。

Abstract:
Objective The tumorigenesis, progression, and metastasis of lung cancer are mostly governed by the immunosuppressive profile. This study aimed to explore the levels of various immunosuppressive inhibitory molecules in lung-cancer patients subjected to different chemotherapy cycles.
Methods Thirty-three patients with advanced lung cancer (ALC; stages III-IV) without receiving prior chemotherapy and 23 healthy subjects were enrolled in our study. Peripheral blood samples were collected from the patients before each chemotherapy cycle. The inhibitory markers expressed in T cells such as TIM3, PD-1, and CTLA4 were analyzed by flow cytometry.
Results The percentages of CD4⁺ TIM3⁺, CD8⁺ TIM3⁺, CD4+ PD-1⁺, CD8⁺ PD-1⁺, CD4⁺ CTLA-4⁺, and CD8⁺ CTLA-4⁺ T cells in the peripheral blood of the ALC patients were significantly higher compared to the controls. The percentage of CD4⁺ TIM3⁺, CD8⁺ TIM3⁺, CD4⁺ PD-1⁺, and CD8⁺ PD-1⁺ T lymphocytes in the peripheral blood of patients (n=19) who achieved PR or SD significantly decreased after five cycles of chemotherapy (P < 0.05). Similarly, the percentages of CD4⁺ CTLA-4⁺ and CD8⁺CTLA-4⁺ T cells in the patients also decreased after five cycles of treatment.
Conclusion The immune status of ALC patients was evidently suppressed. Effective chemotherapy successfully potentiated effective immune responses by downregulating inhibitory molecules in T cells.

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