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

作　　者：许钰杰[1,2] 张毅[1,2,3,4] 邝先奎 段秀芳[1,2] 李洁瑶[1,2] 李建斌[6] 张震[2,3] 张斌[7] 王丽萍[1] 

机构地区：[1]郑州大学第一附属医院肿瘤科,郑州市450052 [2]生物治疗中心 [3]郑州大学生物工程系 [4]河南省高等学校临床医学重点学科开放实验室 [5]河南省项城市第一人民医院肿瘤科 [6]河南省红十字血液中心 [7]美国德州大学圣安东尼奥医学中心医学系

出　　处：《中国肿瘤临床》2013年第16期960-964,共5页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金(编号:81171986);NFSC-NIH生物医学合作项目(编号:812111102);卫生部科学研究基金(编号:20110110001);河南省科技厅基础与前沿技术研究基金(编号:112300410153,122300410155)资助~~

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。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.

关 键 词：晚期肺癌 化疗 流式细胞术 T淋巴细胞 表面抑制分子 

分 类 号：R734.2[医药卫生—肿瘤]