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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。
Objective: To study the effects of Treg cells and Th17 cells on the progression and prognosis of nasopharyngeal carcinoma (NPC) in immune microenvironment. Methods: A total of 557 cases of nasopharyngeal carcinoma confirmed by pathology were collected from January 2001 to December 2003 in Sun Yat-sen University Cancer Center. All patients were initially diagnosed and did not receive any treatment for more than 5 years. Immunohistochemical double staining was used to detect the CD4 and Foxp3, Th17 cell marker CD4 and IL-17 of Treg cells. The numbers of CD4 + Foxp3 + Treg cells, CD4 + IL-17 + Th17 cells in cancer nests And the number of different parts of the interstitial expression, statistical analysis of the number of positive cells and clinicopathological features and prognosis of patients with nasopharyngeal carcinoma. Results: The CD4 + Foxp3 + Treg regulatory T cells mainly infiltrated the tumor stroma (median: 2.0 / HPF). However, no staining of paraffin sections of 557 nasopharyngeal carcinomas was observed with CD4 + IL-17 + Double positive signal. Kaplan-Meier survival curves and log-rank statistical analysis showed that there was a significant positive correlation between CD4 + Foxp3 + Treg regulatory T cells in stroma and tumor-free survival time in NPC patients, but positively correlated with overall survival time Trend, but did not reach statistical significance. The univariate Cox proportional hazards model showed that the high risk of CD4 + Foxp3 + Treg-regulated T cells in tumor stroma was associated with lower recurrence and metastasis than those with fewer tumors, which reduced the risk of death but did not reach Statistical significance. The number of CD4 + Foxp3 + Treg-regulated T cells in NPC was negatively correlated with tumor metastasis and recurrence. Conclusion: The increased number of CD4 + Foxp3 + Treg cells in tumor stroma is positively correlated with the prognosis of patients with nasopharyngeal carcinoma, which can reduce the local recurrence, but can not reduce the risk of death. In the tumor tissues of nasopharyngeal carcinoma, no increase of CD4 + IL-17 + Double positive signal.