Flow Cytometric analysis of Th1 and Th2 cytokines in PBMCs as a parameter of immunological dysfunction in patients of Superficial Transitional cell carcinoma of bladder
Flow Cytometric analysis of Th1 and Th2 cytokines in PBMCs as a parameter of immunological dysfunction in patients of Superficial Transitional cell carcinoma of bladder
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DOI：
10.1007/s00262-005-0045-2
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发表时间：
2006-06-01
影响因子：
5.8
通讯作者：
Saxena, S
中科院分区：
文献类型：
--
作者：
Agarwal, A;Verma, S;Saxena, S
膀胱移行细胞癌（TCC）是最常见的膀胱癌。虽然大多数TCC可以在早期诊断，并容易通过经尿道肿瘤切除术（图尔特）切除，但由于这种癌经常复发，通常在6个月至1年内，因此治疗复杂。Th 1和Th 2免疫应答之间的不平衡已归因于各种恶性肿瘤中的免疫失调。本研究采用流式细胞术检测41例TCC患者（20例复发，21例非复发）外周血单核细胞Th 1/Th 2平衡。它还进一步评估了影响TCC患者和21名正常健康受试者的细胞因子表达和各种细胞表面标志物的抗肿瘤活性的免疫和细胞因素。研究结果显示，发现患者的细胞表面标志物CD 3+、CD 4+和CD 8+沿着NK细胞显著低于健康对照（p < 0.01）。与未复发患者（31.1 +/- 12.27）相比，复发患者（23.9 +/- 9.84）的平均CD 4+表达百分比显著较低。CD 4 + T细胞百分比（平均值+/- SD）产生IFN-γ、IL-2和TNF-α的患者在统计学上显著减少，（19.1 +/- 4.94、52.3 +/- 20.86和12.8 +/- 4.49），与健康对照组相比（分别为23.3 ± 3.67、67.5 ± 12.0和17.6 ± 5.96），（p < 0.01、0.018、0.001）。相反，患者中IL-4、IL-6和IL-10的平均水平（分别为63.8 ± 17.01、60.4 ± 14.79和65.7 ± 14.84）显著高于健康对照组（分别为24.4 ± 8.77、26.5 ± 5.28和20.6 ± 3.81），（p < 0.001）。复发和未复发患者之间的细胞因子表达无统计学显著差异。膀胱癌患者似乎发展为Th 2优势状态，缺乏1型免疫应答。淋巴细胞评估沿着细胞因子测量可以提供用于评估这些患者中细胞介导的免疫功能的灵敏且有价值的工具，并且还可以作为免疫治疗的新靶点在膀胱癌患者的治疗监测中找到应用。
Transitional cell carcinoma (TCC) is the commonest cancer of the bladder. Although majority of TCC can be diagnosed at an early stage and removed easily by transurethral resection of tumor (TURT), the management of this carcinoma is complicated due to frequent recurrences usually within 6 months to one-year period. An imbalance between the Th1 and Th2 immune responses has been attributed to immune dysregulation in various malignancies. The present study aims to evaluate the Th1 and Th2 balance in Peripheral Blood Mononuclear Cells of 41 TCC patients (20 recurrent and 21 non-recurrent) using flow cytometry. It also further assesses immunological and cellular factors influencing the anti-neoplastic activity of the TCC patients and in 21 normal healthy subjects in terms of their cytokine expression and various cell surface markers. The findings of the study revealed that the cell surface markers CD3+, CD4+ and CD8+ along with NK cells were found to be significantly lower in patients than healthy controls (p < 0.01). The mean percent expression of CD4+ was significantly lower in patients showing recurrence (23.9 +/- 9.84) as compared to patients with non-recurrence (31.1 +/- 12.27). The percentage of CD4+T-cells (mean +/- SD) producing IFN-gamma, IL-2 and TNF-alpha were statistically significantly reduced in patients (19.1 +/- 4.94, 52.3 +/- 20.86 and 12.8 +/- 4.49) as compared to healthy controls (23.3 +/- 3.67, 67.5 +/- 12.0 and 17.6 +/- 5.96 respectively), (p < 0.01, 0.018, 0.001). On the contrary, the mean levels of IL-4, IL-6 and IL-10 in patients (63.8 +/- 17.01, 60.4 +/- 14.79 and 65.7 +/- 14.84 respectively) were significantly higher as compared to healthy controls (24.4 +/- 8.77, 26.5 +/- 5.28 and 20.6 +/- 3.81 respectively), (p < 0.001). No statistically significant difference was observed in the cytokine expression between patients showing recurrence and non-recurrence. Patients with bladder cancer seem to develop a Th2 dominant status with a deficient type1 immune response. The lymphocyte evaluation along with cytokine measurement can provide a sensitive and valuable tool for evaluating the function of cell-mediated immunity in these patients and can also find application in therapeutic monitoring of bladder cancer patients as new targets for immunotherapy.