Cancer Immunology Group, Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Immunol Invest. 2013;42(2):81-90. doi: 10.3109/08820139.2012.708376. Epub 2012 Dec 19.
To explore if the increased percentages of Regulatory T (Treg) cells, as well as, overexpression of Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) are involved in laryngeal-squamous cell carcinoma (SCC), 45 patients with laryngeal-SCC and 27 healthy controls were enrolled. Flow cytometry was performed to investigate, in the peripheral blood, the prevalence of CD4+CD25+FoxP3+ Treg cells, as well as, surface and intracellular expression of CTLA-4 by the main lymphocyte subsets (CD4+, CD8+ and CD19+). The results indicated intracellular (In)CTLA4 with considerable higher expression in the CD8+ lymphocytes among patients with laryngeal-SCC compared with the control group (8.2 ± 8.7 versus 2.3 ± 3.5, P = 0.001). The mean percentage of InCTLA4+CD4+ and InCTLA4+CD19+ lymphocytes was also significantly higher in patients (8.7 ± 7.8 versus 4.4 ± 4.2, P = 0.018 and 0.6 ± 0.8 versus 0.2 ± 0.2, P = 0.024, respectively). With respect to surface (Sur)CTLA4, the difference between patients and controls was, however, significant only in the case of CD8+ lymphocytes (0.7 ± 0.6 versus 0.3 ± 0.3, P = 0.003, respectively). The percentage of Treg cells was observed to be significantly higher in patients (7.5 ± 6.3 and 3.2 ± 1.9, P < 0.0001). Furthermore, association analysis revealed the association of Treg cell increase with the higher tumor-size and lymphnode stage (P < 0.005). These data collectively suggest that patients with laryngeal-SCC may benefit from immunotherapy targeting CTLA4 and Treg cells.
为了探究调节性 T（Treg）细胞比例的增加以及细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）的过度表达是否与喉鳞状细胞癌（SCC）有关，我们招募了 45 例喉 SCC 患者和 27 名健康对照者。通过流式细胞术检测外周血中 CD4+CD25+FoxP3+Treg 细胞的流行率，以及主要淋巴细胞亚群（CD4+、CD8+和 CD19+）表面和细胞内 CTLA-4 的表达。结果表明，与对照组相比，喉 SCC 患者的 CD8+淋巴细胞中细胞内（In）CTLA4 的表达明显更高（8.2±8.7 与 2.3±3.5，P=0.001）。InCTLA4+CD4+和 InCTLA4+CD19+淋巴细胞的平均百分比在患者中也显著更高（8.7±7.8 与 4.4±4.2，P=0.018 和 0.6±0.8 与 0.2±0.2，P=0.024，分别）。然而，对于表面（Sur）CTLA4，只有在 CD8+淋巴细胞中，患者与对照组之间的差异才有统计学意义（0.7±0.6 与 0.3±0.3，P=0.003，分别）。患者中 Treg 细胞的百分比明显更高（7.5±6.3 和 3.2±1.9，P<0.0001）。此外，关联分析显示 Treg 细胞增加与肿瘤大小和淋巴结分期较高有关（P<0.005）。这些数据共同表明，喉 SCC 患者可能受益于针对 CTLA-4 和 Treg 细胞的免疫治疗。
