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

Influence of Treg and Th17 Cell in the Tumor Microenvironment on Progression and Prognosis of Nasopharyngeal Carcinoma

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 This study was to investigate the influence of Treg and Th17 Cell on the progression and prognosis of nasopharyngeal carcinoma NPC). Methods 557 nasopharyngeal carcinoma paraffin specimens were collected from January 2001 and December 2003 in cancer center of Sun yat-sen university. All the patients without treatment and with 5 yeas followup were included. Double immunohistochemical staining was performed with CD4/FOXP3 and CD4/IL-17 in 557 patients, statistis analyzed the relationship between the positive cells from different parts with the clinical pathological characteristics and the prognosis of NPC patients. Results We found that CD4+Foxp3+ Treg cell infiltration mostly in the stroma of nasopharyngeal carcinoma median: 2.0/HPF). No co-expression of IL-17 and CD4 was found in NPC TILs by double immunohistochemical staining. Kaplan-Meier survival curve and the log-rank statistical analysis results show that the number of CD4+Foxp3+ Treg cell in stroma were significantly positive correlation with disease-free survival time. Although there is positive correlation with overall survival time trend, but did not reach statistical significance. Single factor Cox proportional hazards model shows that the recurrent and metastasis transfer risk is lower with the more infiltration of CD4+Foxp3+ Treg cell in the stroma than a small number of patients after treatment. CD4+Foxp3+ Treg cell reduce the risk of death to a certain extent in patients, but didnot reach statistical significance. More number of CD4+Foxp3+ Treg cell in the stroma has lower recurrence and metastasis of transfer of patients after treatment in patients than a small number. Conclusion The number of CD4+Foxp3+Treg infiltration in the and stroma of the immune microenvironment was positively related with the prognosis of NPC patients, and it reduce the risk of local recurrence and distant metastasis.