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CTLA-4、PD-1和PD-L1在小细胞肺癌外周血中的分布及临床意义
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Journal Article
CTLA-4、PD-1和PD-L1在小细胞肺癌外周血中的分布及临床意义
2017
Overview
背景与目的本研究旨在探索细胞毒性T淋巴细胞相关抗原（cytotoxic T lymphocyte associated antigen-4,CTLA-4）、程序坏死因子（programmed death 1,PD-1）和程序坏死因子配体（programmed death ligand 1,PD-L1）在小细胞肺癌（small cell lung cancer,SCLC）患者外周血中的分布情况,探索其免疫作用机制并评估其作为生物标志物的临床价值。方法招募290例SCLC患者及60例健康志愿者,收集治疗前和治疗2^nd周期末SCLC患者EDTA抗凝血2 mL。应用流式细胞仪检测CTLA-4、PD-1和PD-L1在外周血CD3、CD4、CD8及CD25的分布,分析其与临床病理特征的相关性;采用细胞免疫化学法和流式细胞法检测PD-L1在SCLC细胞系H446中的表达。结果 SCLC患者外周血中CTLA-4^＋细胞和PD-1^＋细胞水平分别为（1.56±1.24）%和（8.07±3.97）%、CTLA-4在CD3细胞和CD4细胞中的表达水平无明显差异,分别为（4.87±5.18）%和（3.85±2.60）%,均低于PD-1在CD3^＋或CD4^＋细胞中的表达（26.63±9.04）%和（20.79±9.41）%,与健康对照组相比,SCLC中CD4^＋CD25^＋CTLA-4^＋细胞水平明显升高（1.91±1.27）%vs（7.09±5.09）%,P〈0.001;PD-1^＋（CD8^＋）细胞表达水平明显降低,分别为（22.56±4.21）%vs（11.47±5.85）%,P〈0.001。CD4^＋CD25^＋CTLA-4^＋细胞或CD8^＋PD-1^＋细胞水平与患者的年龄、性别、吸烟状况、临床分期以及是否转移等因素无关（P〉0.05）。化疗两周期末CD4^＋CD25^＋CTLA-4^＋和CD8^＋PD-1^＋细胞的水平对比化疗前明显下降,分别为（5.11±2.60）%vs（6.94±4.91）%;（8.74±3.39）%vs（11.48±5.91）%,P值均〈0.000,1,但与无疾病进展生存和总生存无显著相关性。PD-L1高表达于SCLC细胞系H446中并定位在细胞膜和细胞浆,但在外周血中未见表达。结论本研究首次证实SCLC外周血中CTLA4高表达于调节性T细胞中,而PD-1低表达于效应性T细胞,该结果为揭示SCLC免疫
