重组腺病毒p53基因对口腔鳞癌患者外周淋巴细胞亚群的影响

Effect of recombinant adenovirus p53 gene therapy on peripheral blood lymphocyte subsets in patients with oral squamous cell carcinoma

目的:通过观察分析口腔鳞癌患者局部应用rAd-p53后其外周血淋巴细胞亚群比例的变化来探讨rAd-p53对机体细胞免疫水平的影响。方法:实验组12例患者行手术治疗后局部注射重组人腺病毒p53注射液。对照组12例患者仅行手术治疗。所有患者手术前1天、手术后1周均抽取2ml外周血进行淋巴细胞亚群表型分析检测。同时募集了77位健康志愿者,对其外周淋巴细胞亚群进行流式分析。分析比较口腔癌患者与健康志愿者之间、用药组与非用药组之间各淋巴细胞亚群比例变化。结果:口腔癌患者较健康人群总T细胞和辅助性T细胞比例明显降低。活化总T细胞明显增高,静止总T细胞、细胞毒性T细胞比例明显降低。用药组患者治疗后活化总T细胞和细胞毒性T细胞较治疗前均增加,而静止性总T细胞和抑制性T细胞较治疗前降低。相反,对照组的活化总T细胞和细胞毒性T细胞治疗后比例均低于治疗前,同时抑制性T细胞比例也较治疗前增加。结论:口腔癌患者外周淋巴细胞亚群比例分布异常,抗肿瘤细胞免疫功能紊乱,手术不能明显改善患者的抗肿瘤免疫功能,而rAd-p53能调节外周淋巴细胞亚群比例分布。

Objective:To investigate the effect of rAd-p53 on the level of cellular immunity in patients with oral squamous cell carcinoma(OSCC)by observing and analyzing the changes of lymphocyte subsets after local rAd-p53.Methods:A cohort of 36 oral cancer patients was divided into two clinical groups,the experiment group(EG)or the control group(CG),depending on whether or not patients received rAd-p53 treatment.All patients received 2ml peripheral blood one day before surgery and one week after surgery for lymphocyte subgroup phenotype analysis Meanwhile,a total of 77 healthy blood donors were recruitedfor the study.Peripheral blood mononuclear cells(PBMCs)were isolated from venous blood;flow cytometric counts were performed todetect the frequency of peripheral blood lymphocyte subsets,including T-and natural killer(NK)-cell subsets;and correlation analyses with peripheral cellular immune responses and rAd-p53 were performed.Results:The percentages of multipe lymphocyte subsets in oral cancer patients were obviously abnormal when compared with healthy donors,for instance,total T-cells,CD4+helper T cell,cytotoxic T cells,and so on.After treatment,the oral cancer patients received surgery alone had no significant fluctuations in the proportion of any lymphocyte cell subset.rAd-p53-treated patients had an increasing tendency in the mean proportion of activated T cells,cytotoxic T lymphocytes,NK and natural killer-T(NKT)cells,and a decreased percentage of total T-cells,CD4+helper T cell,inactive T cells and suppressor T lymphocytes in their PBMCs.However,except for inactive T cells,the differences of all subsets did not reach statistical significance.Conclusion:Patients with oral cancer have compromised anti-tumor cellular immunity,and surgery typically does not improve anti-tumor immunity within a short time period,whereas regional injection of rAd-p53 as adjuvant therapy for cancer surgery could enhance anti-tumor immunity.