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肿瘤相关巨噬细胞和调节性 T 细胞在 EBV 阳性和 EBV 阴性鼻咽癌中的预后作用。

Prognostic role of tumour-associated macrophages and regulatory T cells in EBV-positive and EBV-negative nasopharyngeal carcinoma.

机构信息

Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.

Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

出版信息

J Clin Pathol. 2018 Mar;71(3):267-274. doi: 10.1136/jclinpath-2017-204664. Epub 2017 Sep 6.

Abstract

AIMS

Tumour-associated macrophages (TAMs) and regulatory T cells (Tregs) form a special niche supporting tumour progression, and both correlate with worse survival in head and neck cancers. However, the prognostic role of TAM and Tregs in nasopharyngeal carcinoma (NPC) is still unknown. Therefore, we determined differences in TAMs and Tregs in different NPC subtypes, and their prognostic significance.

METHODS

Tissue of 91 NPCs was assessed for TAMs and Tregs by determination of CD68, CD163, CD206 and FOXP3 expression in the tumour microenvironment. Clinicopathological correlations were assessed using Pearson X test, Fisher's exact test, analysis of variance and Mann-Whitney U test. Survival was analysed using Kaplan-Meier curves and Cox regression.

RESULTS

CD68 and FOXP3 counts were higher in Epstein-Barr virus (EBV)-positive NPC, while CD68-/FOXP3-, CD163+/FOXP3- and CD206+/FOXP3- infiltrates were more common in EBV-negative NPC. In the whole NPC group, CD68-/FOXP3- correlated with worse overall survival (OS), and after multivariate analysis high FOXP3 count showed better OS (HR 0.352, 95% CI 0.128 to 0.968). No difference in M2 counts existed between EBV-positive and negative NPC.

CONCLUSIONS

FOXP3, a Treg marker, seems to be an independent prognostic factor for better OS in the whole NPC group. Therefore, immune-based therapies targeting Tregs should be carefully evaluated. M2 spectrum macrophages are probably more prominent in EBV-negative NPC with also functional differences compared with EBV-positive NPC.

摘要

目的

肿瘤相关巨噬细胞(TAMs)和调节性 T 细胞(Tregs)形成了一个特殊的微环境,支持肿瘤的进展,两者与头颈部癌症的生存率降低相关。然而,TAMs 和 Tregs 在鼻咽癌(NPC)中的预后作用尚不清楚。因此,我们确定了不同 NPC 亚型中 TAMs 和 Tregs 的差异及其预后意义。

方法

通过检测肿瘤微环境中 CD68、CD163、CD206 和 FOXP3 的表达,评估 91 例 NPC 组织中的 TAMs 和 Tregs。采用 Pearson X 检验、Fisher 确切检验、方差分析和 Mann-Whitney U 检验评估临床病理相关性。采用 Kaplan-Meier 曲线和 Cox 回归分析生存情况。

结果

EBV 阳性 NPC 中 CD68 和 FOXP3 计数较高,而 EBV 阴性 NPC 中 CD68-/FOXP3-、CD163+/FOXP3-和 CD206+/FOXP3-浸润更为常见。在整个 NPC 组中,CD68-/FOXP3-与总生存期(OS)较差相关,多变量分析显示 FOXP3 计数高与 OS 较好相关(HR 0.352,95%CI 0.128 至 0.968)。EBV 阳性和阴性 NPC 之间 M2 计数无差异。

结论

Treg 标志物 FOXP3 似乎是整个 NPC 组中 OS 的独立预后因素。因此,针对 Tregs 的免疫治疗方法应仔细评估。与 EBV 阳性 NPC 相比,EBV 阴性 NPC 中可能更突出 M2 谱巨噬细胞,并且具有功能差异。

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