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

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。

Objective： The tumorigenesis, progression, and metastasis of lung cancer are mostly governed by the immunosuppres- sive profile. This study aimed to explore the levels of various immunosuppressive inhibitory molecules in lung-cancer patients subject- ed 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 be- fore each chemotherapy cycle. The inhibitory markers expressed in T cells such as TIM3, PD-1, and CTLA4 were analyzed by flow cy- tometry. Results： The percentages ofCD4＋ 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 CD4t 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 de- creased after five cycles of chemotherapy （P〈0.05）. Similarly, the percentages of CD4＋ CTLA-4＋ and CD8＋CTLA-4＋ T cells in the pa- tients also decreased after five cycles of treatment. Conclusion： The immune status of ALC patients was evidently suppressed. Effec- tive chemotherapy successfully potentiated effective immune responses by downregulating inhibitory molecules in T cells.