天津医药

天津医药 ›› 2015, Vol. 43 ›› Issue (9): 1026-1030.doi: 10.11958/j.issn.0253-9896.2015.09.019

• 专题研究肿瘤基因与临床 • 上一篇    下一篇

调节性T细胞、CD8+T细胞在恶性黑色素瘤免疫微环境中的表达及其临床意义

苏月颖， 安秀梅， 赵华， 魏枫， 张新伟△   

  1. 天津医科大学肿瘤医院免疫室、 国家肿瘤临床医学研究中心、 天津市肿瘤免疫与生物治疗重点实验室 （邮编300060）
  • 收稿日期:2014-12-10 修回日期:2015-03-22 出版日期:2015-09-15 发布日期:2015-09-15
  • 通讯作者: 张新伟 E-mail:zhangxinwei@tjmuch.com
  • 作者简介:苏月颖 （1988）， 女， 硕士在读， 主要从事恶性黑色素瘤免疫微环境的研究
  • 基金资助:
    973子课题基于纳米技术的肺癌早期检测研究资助项目 （2012CB9333004）； 国家自然科学基金资助项目 （81171983）； 天津市科委应用基础面上项目资助项目 （12JCYBJC16100）

The expression of Tregs and CD8+ T cells in malignant melanoma and its relationship with prognosis

SU Yueying, AN Xiumei, ZHAO Hua, WEI Feng, ZHANG Xinwei△   

  • Received:2014-12-10 Revised:2015-03-22 Published:2015-09-15 Online:2015-09-15

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摘要：  目的 探讨调节性 T 细胞 （Tregs） 和 CD8+ T 细胞在黏膜恶性黑色素瘤和肢端恶性黑色素瘤局部免疫微环境中表达情况的差异， 及其与患者预后的关系。方法 采用免疫组织化学染色法对 58 例恶性黑色素瘤组织进行染色， 检测 Foxp3+ Tregs 和 CD8+ T 细胞的浸润情况， 分析两者与临床病理指标及预后的相关性。结果 Foxp3 与 CD8+ T 细胞阳性表达无相关关系。黏膜恶性黑色素瘤组织中 Foxp3+ Tregs 数量明显高于肢端恶性黑色素瘤 （t=2.648， P= 0.011）； 肿瘤直径≥3 cm、 有淋巴结转移、 有远处转移的恶黑患者 Foxp3high Tregs 相对较高 （P＜0.05）。存在溃疡的恶性黑色素瘤患者中， CD8high 组所占比例明显高于无溃疡者 （33.3% vs 5.9%， P＜0.05）。Foxp3high 组的中位无进展生存期（PFS） 是 12 个月， 明显低于 Foxp3low 组 （31 个月）； CD8high 组的中位 PFS 是 25 个月， 明显高于 CD8low 组 （中位 PFS 12 个月）； 亚组分析显示 Foxp3high CD8low 组患者中位 PFS 是 7 个月， 明显低于 Foxp3high CD8high 组 （25 个月）、 Foxp3low CD8low 组（18 个月） 以及 Foxp3low CD8high 组 （59 个月）。不同肿瘤位置、 Foxp3+ Treg 数量、 CD8+ T 细胞数量、 有无远处转移的恶性黑色素瘤患者中位 PFS 不同。结论 Tregs 的数量与恶性黑色素瘤的进展密切相关， 黏膜恶性黑色素瘤预后欠佳可能与Tregs 浸润有关。

关键词:  黑色素瘤, T 淋巴细胞, CD8阳性 T 淋巴细胞, 肿瘤逃逸, 预后

Abstract: Objective To investigate the different distribution of regulatory T cells (Tregs) and CD8+ T cells in the local immune microenvironment of mucosal malignant melanoma and cutaneous malignant melanoma, and analyze the relationship between the two indicators and the prognosis of patients. Methods Immunohistochemistry staining was used to assess the ex⁃ pression of Foxp3+ Tregs and CD8+ T cells in tumor microenvironment of 58 patients with malignant melanoma. The correlation between two factors, clinicopathological characteristics, and prognosis were analyzed. Results There is no correlation be⁃ tween the expression of Foxp3 and CD8. The number of Foxp3+ Tregs was significantly higher in mucosa malignant melanoma than that in cutaneous malignant melanoma (t=2.648, P=0.011). The proportion of Foxp3high Tregs was significantly higher in pa⁃ tients with tumor diameter ≥3 cm, lymph node metastasis and distant metastasis than that in patients with tumor diameter＜3 cm, no lymph node metastasis and no distant metastasis (P＜0.05). In addition, in patients with ulceration that proportion was significantly higher in CD8high group than that in patients without ulceration (33.3% vs 5.9%, P＜0.05). The median progres⁃ sion-free surial (PFS) was 12 months in Foxp3high group, which was significantly longer than that of Foxp3low group (31 months, P＜0.05). The median PFS was significantly higher in CD8high group (25 months) than that of CD8low group (12 months, P＜ 0.05). Subgroup analysis showed that the median PFS was 7 months in Foxp3high CD8low group, which was significantly lower than that of Foxp3high CD8high group (25 months) and Foxp3low CD8low group (18 months, P=0.003). Univariate analysis showed that median PFS was different in patients with different tumor location, different number of Foxp3+ Treg, different number of CD8+ T cells, and distant metastases. Conclusion The number of Tregs is closely associated with metastasis in patients with malig⁃ nant melanoma. Compared with cutaneous malignant melanoma, our results indicate that the poor prognosis of mucosal malig⁃ nant melanoma may be associated with the infiltration of more Tregs.

Key words: melanoma, T-lymphocytes, CD8-positive T-lymphocytes, tumor escape, prognosis