Tumor-infiltrating CD4⁺ CD25⁺ FOXP3⁺ Treg is associated with plasma EBV DNA and disease progression in nasopharyngeal carcinoma.

IF 3.1 2区医学 Q3 IMMUNOLOGY

Infectious Agents and Cancer Pub Date : 2025-05-09 DOI:10.1186/s13027-025-00660-4

Enzi Feng, Yaoyu Yang, Jie Yang, Rongyi Hu, Ling Tian, Xinyu Yang, Meng Yang, Qianqian Qu, Yanxin Ren, Xiaojiang Li

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引用次数: 0

Abstract

Background: Regulatory T cells (Tregs) play a significant role in immune evasion within the tumor microenvironment (TME). Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV) infection. Previous studies have shown that EBV can suppress immune activity. The relationship between plasma EBV DNA levels and Treg infiltration in NPC remains to be elucidated. Some studies have shown that FOXP3, a Treg marker, is a favorable prognostic factor in NPC. However, relying solely on FOXP3 for Treg identification may be unreliable due to its expression in other cell types. Therefore, this study investigated the impact of tumor-infiltrating Tregs identified by CD4, CD25, and FOXP3 triple markers in NPC and the relationship between these Tregs and EBV infection.

Methods: In this study, 103 NPC patients were included. All tumor slides were stained using multi-immunofluorescence with CD4, CD25, and FOXP3. HALO software was used to analyze whole-slide images. The correlation between two factors was assessed using Spearman analysis. The prognostic value of factors was evaluated using Kaplan-Meier curves and Cox regression.

Results: A significant positive correlation was observed between Treg infiltration in tumor tissues and plasma EBV DNA levels (r = 0.3428, p = 0.02). Higher Treg infiltration was significantly associated with poorer progression-free survival (PFS) (p = 0.03) and was an independent risk factor for NPC progression (p = 0.045). CD25 expression was positively correlated with plasma EBV DNA levels (r = 0.3229, p = 0.03). Furthermore, increased Treg infiltration was negatively correlated with peripheral CD8⁺ T cells (r=-0.3556, p = 0.006). The proportion of peripheral CD8⁺ T cells in patients with advanced-stage NPC was significantly lower compared to those with early stage (p = 0.02).

Conclusion: This study identified tumor-infiltrating CD4⁺CD25⁺FOXP3⁺ Tregs as an independent negative prognostic factor for NPC progression and found higher Treg infiltration positively associated with plasma EBV DNA levels.

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肿瘤浸润性CD4+ CD25+ FOXP3+ Treg与鼻咽癌血浆EBV DNA和疾病进展相关

背景：调节性T细胞（Regulatory T cells, Tregs）在肿瘤微环境（tumor microenvironment， TME）免疫逃避中发挥重要作用。鼻咽癌（NPC）与eb病毒（EBV）感染密切相关。先前的研究表明，EBV可以抑制免疫活性。鼻咽癌患者血浆EBV DNA水平与Treg浸润的关系尚不清楚。一些研究表明Treg标志物FOXP3是鼻咽癌的有利预后因素。然而，由于FOXP3在其他细胞类型中也有表达，因此仅依靠FOXP3进行Treg鉴定可能不可靠。因此，本研究探讨了由CD4、CD25和FOXP3三重标记物鉴定的肿瘤浸润性Tregs在鼻咽癌中的影响，以及这些Tregs与EBV感染的关系。方法：本研究纳入103例鼻咽癌患者。所有肿瘤切片均采用CD4、CD25和FOXP3多重免疫荧光染色。采用HALO软件对全片图像进行分析。使用Spearman分析评估两个因素之间的相关性。采用Kaplan-Meier曲线和Cox回归评价各因素的预后价值。结果：肿瘤组织Treg浸润与血浆EBV DNA水平呈显著正相关（r = 0.3428, p = 0.02）。较高的Treg浸润与较差的无进展生存期（PFS）显著相关（p = 0.03），并且是NPC进展的独立危险因素（p = 0.045）。CD25表达与血浆EBV DNA水平呈正相关（r = 0.3229, p = 0.03）。Treg浸润增加与外周血CD8+ T细胞呈负相关（r=-0.3556, p = 0.006）。晚期鼻咽癌患者外周血CD8+ T细胞比例明显低于早期鼻咽癌患者（p = 0.02）。结论：本研究发现肿瘤浸润CD4+CD25+FOXP3+ Tregs是鼻咽癌进展的一个独立的阴性预后因素，并且发现较高的Treg浸润与血浆EBV DNA水平呈正相关。

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来源期刊

Infectious Agents and Cancer ONCOLOGY-IMMUNOLOGY

CiteScore

5.80

自引率

2.70%

发文量

期刊介绍： Infectious Agents and Cancer is an open access, peer-reviewed online journal that encompasses all aspects of basic, clinical, epidemiological and translational research providing an insight into the association between chronic infections and cancer. The journal welcomes submissions in the pathogen-related cancer areas and other related topics, in particular: • HPV and anogenital cancers, as well as head and neck cancers; • EBV and Burkitt lymphoma; • HCV/HBV and hepatocellular carcinoma as well as lymphoproliferative diseases; • HHV8 and Kaposi sarcoma; • HTLV and leukemia; • Cancers in Low- and Middle-income countries. The link between infection and cancer has become well established over the past 50 years, and infection-associated cancer contribute up to 16% of cancers in developed countries and 33% in less developed countries. Preventive vaccines have been developed for only two cancer-causing viruses, highlighting both the opportunity to prevent infection-associated cancers by vaccination and the gaps that remain before vaccines can be developed for other cancer-causing agents. These gaps are due to incomplete understanding of the basic biology, natural history, epidemiology of many of the pathogens that cause cancer, the mechanisms they exploit to cause cancer, and how to interrupt progression to cancer in human populations. Early diagnosis or identification of lesions at high risk of progression represent the current most critical research area of the field supported by recent advances in genomics and proteomics technologies.