DC-CIK 生物治疗后肺癌患者Pro-GRP 和T 淋巴 细胞亚群对免疫功能评价的临床意义

Value of Pro-GRP and T lymphocyte subsets in assessment of immune functions of lung cancer patients after DC-CI biological therapy

摘要:

目的 探讨生物治疗前后肺癌患者胃泌素释放肽前体（Pro-GRP）和T 淋巴细胞亚群对免疫功 能评价的临床意义，方法 选取2014 年9 月-2015 年8 月天津市第五中心医院收治经病理确诊的肺癌患者45 例，根据病理组织学分为小细胞肺癌组（SCLC）和非小细胞肺癌组（NSCLC），选取同期健康体检者40 例为 对照组。采用贝克曼- 库尔特FC500 流式细胞仪检测受检者外周血CD3+、CD4+、CD8+、调节性T 细胞（Treg）， 采用德国罗氏COBAS 6000 检测受检者外周血的Pro-GRP、神经元特异性烯醇化酶（NSE）、癌胚抗原（CEA）、 细胞角蛋白19 的可溶性片段（CYFAR21-1），化疗结束后，联合生物治疗DC-CIK 自体细胞回输3 个周期后， 用相同方法采集患者静脉血，检测Pro-GRP、T 淋巴细胞亚群、Treg。结果 DC-CIK 细胞生物治疗后NSCLC 组CD8+T 淋巴细胞和Treg 细胞较治疗前下降，CD3+、CD4+T 淋巴细胞、CD4+/CD8+ 比值较治疗前上升； SCLC 组CD3+、CD4+、CD8+ T 淋巴细胞数量较治疗前增加，Treg 细胞较治疗前下降；Pro-GRP 各组均较治疗 前下降；Pro-GRP 与T 淋巴细胞亚群在SCLC 组呈负相关，在NSCLC 组无相关；Pro-GRP 与Treg 细胞在各 组呈正相关（P <0.05）。结论 Pro-GRP 在SCLC 患者与T 淋巴细胞亚群存在相关性，可用于辅助早期临床 诊断，并与T 淋巴细胞亚群共同评价患者的免疫调节功能，DC-CIK 细胞回输生物治疗可增强患者特异性杀伤 肿瘤的能力，提高机体的免疫监视功能，抑制肿瘤免疫逃逸，改善患者的免疫功能。

Abstract:

Objective To discuss the clinical meanings of Pro-GRP and T lymphocyte subpopulation for the assessment of immune functions of lung cancer patients before and after biological therapy. Methods Forty-five lung cancer patients from Tianjin Fifth Central Hospital from September 2014 to August 2015 were recruited and divided into small cell lung cancer (SCLC) group and non-small cell lung cancer (NSCLC) group according to the pathological histology. Forty healthy people having physical examination at the same period were enrolled as the control group. Beckman Coulter FC500 flow cytometry was adopted to detect the CD3+, CD4+, CD8+ and regulatory T cells (Treg) in the peripheral blood. COBAS6000 produced by Germany-based Roche was used to detect the Pro- GRP, neuron-specific enolase (NSE), CEA and cytokeratin 19 fragment (CYFAR21-1) in the peripheral blood. After chemical therapy and three cycles of combined biological therapy of successive retransformation of DCCIK autologous cells , the same method was used to collect the venous blood of the patients to detect Pro-GRP, T lymphocyte subpopulation and Treg. Results After DC-CIK cell biological therapy, CD8+ T lymphocytes and Treg cells decreased, and its CD3+, CD4+ T lymphocytes and CD4+/CD8+ ratio increased in the NSCLC group compared to those before treatment (P < 0.05); CD3+, CD4+ and CD8+ T lymphocytes increased and Treg cells decreased in the SCLC group compared with those before treatment (P < 0.05). In each group, Pro-GRP decreased after treatment compared with that before treatment (P < 0.05). There were obvious negative correlations between Pro-GRP and T lymphocyte subsets in the SCLC group (P < 0.05) but not in the NSCLC group (P > 0.05); there was a positive correlation between Pro-GRP and Treg cells in each group with significant difference (P < 0.05). Conclusions Pro- GRP is correlated with T lymphocyte subsets in the patients with small cell lung cancer. It can assist the early clinical diagnosis and along with T lymphocyte subpopulation it can be used to assess the immune regulatory function of the patients. DC-CIK cell retransformation biological therapy enhances patients’ specific ability of killing tumors, improves the immune surveillance function, restrains the immune escape of tumor and improves patients’ immune functions.