Significance of Dynamic Monitoring of T Lymphocyte Subsets and NK Cells in Patients with Esophageal Cancer before and after the Surgery and Chemotherapy
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摘要:
目的 探讨在食管癌患者手术及化疗前后对外周血T淋巴细胞亚群及NK细胞水平进行多时间点检测的价值及临床意义。 方法 采用流式细胞技术检测39例食管癌患者在手术及化疗前后外周血T淋巴细胞亚群和NK细胞的百分率，并与健康对照组比较并进行统计学分析。 结果 食管癌患者T淋巴细胞不同的亚群及NK细胞水平与正常人群相比差异有统计学意义（P < 0.05）；手术后T淋巴细胞各亚群及NK细胞水平均较术前明显下降（P < 0.05），且在术后第3天为最低值，随后逐渐升高，但CD4+/CD8+未见明显变化；患者化疗后CD3+、CD4+比例及CD4+/CD8+有所升高，而CD8+比例下降，差异有统计学意义（P < 0.05），在化疗后3周各T淋巴细胞亚群比例与化疗前相似，化疗前后NK细胞水平虽表现出与CD3+、CD4+类似的变化趋势，但是并不显著。 结论 食管癌患者的免疫功能处于受抑制的状态，手术后免疫功能更是出现一过性降低，化疗能够一定程度上改善这种状态，但长期来看，化疗对T淋巴细胞亚群及NK细胞水平的影响可能很小，这可能支持化疗与T细胞依赖性免疫治疗在同步或序贯方案中有效结合的观点。 Abstract:Objective To explore the clinical value of peripheral blood T lymphocyte subsets and NK cell levels measured at multi-time points in patients with esophageal cancer. Methods A total of 39 cases of esophageal cancer patients were enrolled. Flow cytometry was used to detect the T lymphocyte subsets and NK cells in peripheral blood before and after the surgery and chemotherapy. Another 39 cases of healthy adults in the clinic during the same period were included as the control group, and the level of T lymphocyte subsets and NK cells were detected in the same way. Results The proportions of lymphocytes subsets and the levels of NK cells in patients with esophageal cancer were significantly lower compared with the control group before the surgery and chemotherapy （P < 0.05）, and decreased significantly after the surgery （P < 0.05）, the lowest value was found on the 3rd day after the surgery, then increased gradually, the ratio of CD4+/CD8+ didn’ t show the obvious difference in this period. After the chemotherapy, the proportion of CD3+、CD4+ and the ratio of CD4+/CD8+ increased significantly, while the proportion of CD8+ decreased significantly （P < 0.05）. 3 weeks after the chemotherapy, the proportions of T lymphocyte subsets were similar to that before the chemotherapy. There was no significant difference in NK cells though it showed a similar trend as T lymphocyte subsets before and after the chemotherapy （P > 0.05）. Conclusion The immune function of patients with esophageal cancer is in a suppressed state. After the surgery, their immune function reduced temporarily. Chemotherapy can improve this situation but it actually useful in the long term, which may support the idea of effective combinations of chemotherapy and T cell-dependent immunotherapy in a simultaneous or sequential regimen. -
Key words:
- Esophageal cancer /
- T lymphocyte subsets /
- NK cell /
- Surgery /
- Chemotherapy
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图 1 食管癌组术前、术后T细胞亚群及NK细胞水平变化趋势图
Figure 1. The trend of T lymphocyte subsets and the levels of NK cells before and after surgery
图 2 食管癌组化疗前后T细胞亚群及NK细胞水平变化趋势图
Figure 2. The trend of T lymphocyte subsets and the levels of NK cells before and after chemotherapy
表 1 患者基本信息（n）
Table 1. Clinical and pathological characteristics of patients enrolled in the study （n）
项目 食管癌组 正常对照组 性别（男/女） 37/2 35/4 年龄（${{\bar x} } \pm s$），岁 58.38 ± 7.48 55.50 ± 11.00 病例类型 鳞癌 39 腺癌 0 分化程度 低 9 中-低 19 中 10 中-高 1 高 0 TNM分期 Ⅰ 0 Ⅱ 29 Ⅲ 10 Ⅳ 0 
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表 2 食管癌组术前与对照组T细胞亚群及NK细胞水平的比较（
$\bar{x} \pm s$ ）Table 2. The proportions of lymphocytes subsets and the levels of NK cells in healthy controls and in patients with esophageal cancer before surgery （
$\bar{x} \pm s$ ）组别 CD3+ CD4+ CD8+ NK细胞 CD4+/CD8+ 正常对照组 72.02 ± 5.76 44.52 ± 5.15 25.96 ± 7.01 17.55 ± 6.70 1.71 ± 0.52 食管癌组 67.40 ± 8.11 38.10 ± 9.60 28.25 ± 3.74 14.46 ± 7.55 1.35 ± 0.28 t 2.497 6.413 2.232 2.843 4.834 P 0.025 0.008 0.032 0.014 < 0.001
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表 3 食管癌组术前、术后T细胞亚群及NK细胞水平的变化（
$\bar{x} \pm s$ ）Table 3. The proportions of lymphocytes subsets and the levels of NK cells before and after surgery （
$\bar{x} \pm s$ ）时间点 CD3+ CD4+ CD8+ NK细胞 CD4+/CD8+ 手术前 67.40 ± 8.11 38.10 ± 9.60 28.25 ± 3.74 14.46 ± 7.55 1.35 ± 0.28 手术后3 d 52.56 ± 6.29* 26.17 ± 3.45* 18.36 ± 4.26* 9.69 ± 3.27* 1.42 ± 0.58 手术后7 d 58.33 ± 7.08* 31.67 ± 7.39* 22.05 ± 4.27* 12.42 ± 6.25* 1.43 ± 0.75 F 24.985 44.659 25.476 65.440 1.290 P < 0.001 < 0.001 < 0.001 < 0.001 0.533 与手术前比较，*P < 0.05。
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表 4 食管癌组化疗前后T细胞亚群水平的变化（
$\bar{x} \pm s$ ）Table 4. The proportions of T lymphocyte subsets and NK cells in patients with esophageal cancer before and after chemotherapy （
$\bar{x} \pm s$ ）时间点 CD3+ CD4+ CD8+ NK细胞 CD4+/CD8+ 化疗第一周期前 66.33 ± 4.98 38.00 ± 6.03 27.94 ± 8.16 14.41 ± 6.34 1.36 ± 0.81 化疗后1周 69.81 ± 5.79# 41.96 ± 11.21# 25.02 ± 5.05# 14.75 ± 4.49 1.68 ± 0.79# 化疗后3周 67.04 ± 9.46 38.80 ± 9.41 27.48 ± 6.13 14.30 ± 6.02 1.41 ± 0.93 F 21.012 25.231 18.439 0.646 2.655 P < 0.001 < 0.001 0.003 0.593 0.049 与化疗前比较，#P < 0.05。
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