肿瘤微环境中Treg细胞和Th17细胞对鼻咽癌进展和预后的影响

发布时间：2018-12-29 18:04

【摘要】：目的:研究免疫微环境中Treg细胞和Th17细胞对鼻咽癌(Nasopharyngeal carcinoma,NPC)进展和预后的影响。方法:收集2001年1月~2003年12月在中山大学肿瘤防治中心经病理证实为鼻咽癌的石蜡标本557例。所有患者均为初次诊断且未进行任何治疗,随访时间均超过5年。采用免疫组化双染色法检测Treg细胞分子标志物CD4和Foxp3、Th17细胞分子标志物CD4和IL-17,观察并计数,CD4+Foxp3+Treg细胞、CD4+IL-17+Th17细胞在癌巢和间质不同部位的表达数目,统计分析其阳性细胞数目与临床病理特征及与鼻咽癌患者预后的关系。结果:CD4+Foxp3+Treg调节性T细胞主要在肿瘤间质浸润(中位数:2.0/HPF),然而,在557例鼻咽癌组织石蜡切片染色中均未观察到CD4+IL-17+双阳性信号。Kaplan-Meier生存曲线和log-rank统计分析结果表明,间质中的CD4+Foxp3+Treg调节性T细胞与鼻咽癌患者的无瘤生存时间显著正相关,而与总体生存时间虽然存在正相关趋势,但没有达到统计学意义。单因素Cox比例风险模型显示,肿瘤间质中CD4+Foxp3+Treg调节T细胞高数量组发生治疗后转移复发的风险低于数量较少的患者,能一定程度降低患者的死亡风险,但没有达到统计学意义。CD4+Foxp3+Treg调节T细胞在NPC间质中的数量与肿瘤转移复发呈负相关。结论:肿瘤间质中CD4+Foxp3+Treg细胞浸润数量增多与鼻咽癌患者预后呈正相关,降低局部复发,但不能降低死亡风险;在鼻咽癌肿瘤组织中未观察到CD4+IL-17+双阳性信号。
[Abstract]:Aim: to study the effects of Treg cells and Th17 cells in immune microenvironment on the progression and prognosis of nasopharyngeal carcinoma (Nasopharyngeal carcinoma,NPC). Methods: from January 2001 to December 2003, 557 paraffin wax specimens of nasopharyngeal carcinoma were collected from Cancer Center of Sun Yat-sen University. All patients were diagnosed for the first time without any treatment and followed up for more than 5 years. The expression of Treg cell marker CD4 and Foxp3,Th17 cell molecular marker CD4 and IL-17, were observed and counted by immunohistochemical double staining method. The expression of CD4 Foxp3 Treg cells and CD4 IL-17 Th17 cells in different parts of cancer nest and stroma were detected and counted. The relationship between the number of positive cells and clinicopathological features and prognosis of nasopharyngeal carcinoma was analyzed statistically. Results: CD4 Foxp3 Treg regulatory T cells were mainly infiltrated in the stroma (median: 2.0/HPF), however, CD4 IL-17 double positive signals were not observed in the paraffin sections of 557 nasopharyngeal carcinoma tissues. The Kaplan-Meier survival curve and log-rank statistical analysis showed that there were no CD4 IL-17 positive signals in 557 nasopharyngeal carcinoma tissues. The CD4 Foxp3 Treg regulatory T cells in the stroma were positively correlated with the tumor-free survival time of nasopharyngeal carcinoma patients, while there was a positive correlation with the overall survival time, but there was no statistical significance. Univariate Cox proportional risk model showed that the risk of metastasis and recurrence in the tumor stroma with high number of T cells regulated by CD4 Foxp3 Treg was lower than that in the patients with a small number of tumor cells, and the risk of death could be reduced to a certain extent. The number of T cells regulated by CD4 Foxp3 Treg in the stroma of NPC was negatively correlated with tumor metastasis and recurrence. Conclusion: the increase of CD4 Foxp3 Treg cell infiltration in the tumor stroma is positively correlated with the prognosis of nasopharyngeal carcinoma and decreases the local recurrence, but does not reduce the risk of death, and no CD4 IL-17 double positive signal is observed in the tumor tissue of nasopharyngeal carcinoma.
【作者单位】：南华大学附属第一医院放疗科;中山大学肿瘤防治中心;南华大学医学院肿瘤研究所;
【基金】：国家基础研究发展计划(973计划)(2013CB910301) 国家自然科学基金项目(81272960) 湖南省卫生厅项目(B2014-051) 湖南省自然基金项目(S2016J504B) 湖南省重点项目(2013WK2010)
【分类号】：R739.63

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