CD4^+CD25^+Foxp3^+调节性T细胞在鼻腔鼻窦鳞状细胞癌中的表达和免疫抑制功能研究

Frequency and suppressive capacity of CD4^+CD25^+Foxp3^+ regulatory T cells in sinonasal squamous cell carcinoma

目的分析鼻腔鼻窦鳞状细胞癌中CD4+CD25+Foxp3+调节性T细胞的表达数量,并评估其免疫抑制功能。方法入选鼻腔鼻窦鳞状细胞癌患者(均为T1-2N0M0)和正常对照者各15例,分别采集研究对象外周血标本、患者肿瘤组织及正常对照者鼻黏膜组织。应用流式细胞术分析组织匀浆和外周血中调节性T细胞、Th1细胞和Th2细胞数量。免疫组化染色计数局部组织内调节性T细胞数量。将外周血调节性T细胞与外周血效应性T细胞共培养,72 h后采集细胞培养上清液,应用ELISA方法检测IFN-γ和IL-4水平,比较两组患者调节性T细胞的免疫抑制功能。结果鳞癌组肿瘤组织内调节性T细胞、Th2细胞数量显著高于正常鼻黏膜,而Th1细胞数量显著降低。与正常对照组相比,鳞癌组患者外周血中调节性T细胞增加,Th1细胞减少,Th2细胞无显著差异。外周血调节性T细胞对T h1细胞的抑制功能在鳞癌组较正常对照组增强。结论鼻腔鼻窦鳞状细胞癌肿瘤组织内和外周血中的调节性T细胞数量升高、对Th1细胞免疫抑制能力增强。调节性T细胞参与鼻腔鼻窦鳞状细胞癌的肿瘤局部免疫和全身免疫调节,可作为预后的生物学指标之一。

OBJECTIVE This study was aimed to evaluate the f requency and suppressive capacity of regulatory T(Treg) cells i n sinonasal squamous cell carcinoma(SSCC). METHODS Frequency of Treg, Th1 and Th2 cells were evaluated by flow cytometry in tissue homogenate and peripheral blood from 15 SSCC patients and 15 normal controls. Local CD4+Foxp3+ T cells were assessed by immunohistochemistry. Tregs were tested for regulatory function by co-culture with effector T cells. Cell culture supernatant was collected after 72 hours. IFN-γ and IL-4 were analysed using ELISA method. RESULTS Tumorinfiltrating Tregs and Th2 cells increased significantly from normal to SSCC, whereas Th1 cells decreased significantly. Significantly elevated frequency and enhanced suppression capacity of circulating Treg cells in SSCC were detected compared with healthy controls, concomitant with Th1 decrease. CONCLUSION Frequency and suppressive capacity of Tregs enhanced with progression of malignancy from normal to SSCC. Treg cells play a role in both local and systemic immune response in SSCC. Functional Tregs accumulation in the peripheral blood and/or at the tumor site of patients may be used as a biomarker for poor prognosis.