鼻咽癌患者中表达TNFR2的CD4+ FoxP3+ 调节性T细胞的异常频率。
Aberrant frequency of TNFR2-expressing CD4+ FoxP3+ regulatory T cells in nasopharyngeal carcinoma patients.
发表日期:2023 Aug 30
作者:
Engku Nur Syafirah Engku Abd Rahman, Ahmad Adebayo Irekeola, Rafidah Hanim Shueb, Norhafiza Mat Lazim, Rohimah Mohamud, Xin Chen, Liyana Ghazali, Nik Mohd Syahrul Hafizzi Awang, Ali Haron, Yean Yean Chan
来源:
Parasites & Vectors
摘要:
TNFR2是CD4+ FoxP3+ 调节性T细胞(Tregs)高度抑制性亚群的表面标记,适用于人类和小鼠。本研究检测了鼻咽癌(NPC)患者和健康对照组中Tregs的TNFR2表达情况。评估了TNFR2+ Tregs的增殖、迁移、存活情况以及与临床病理特征的关联。还确定了选定细胞因子的表达水平。结果显示,在NPC患者的外周血(PB)(10.45 ± 5.71%)和肿瘤微环境(TME)(54.38 ± 16.15%)中,Tregs的TNFR2表达水平明显高于常规T细胞(Tconvs)(3.91 ± 2.62%,p < 0.0001),与健康对照组相似。 在NPC PB中,TNFR2表达水平(1.06 ± 0.99%)与CD25+(0.40 ± 0.46%)和CD127-/low(1.00 ± 0.83%)相比与FoxP3的表达更为相关(p = 0.0005)。尽管TNFR2的表达与Tregs的功能能力(增殖、迁移和存活)之间并没有显著关联(p > 0.05),但NPC患者PB和TME的TNFR2+ Tregs的比例显示出更高的增殖能力、更高的迁移能力和更好的存活能力,相比健康对照组。此外,NPC患者的TNFR2+ Tregs表达的IL-6(p = 0.0077)、IL-10(p = 0.0001)、IFN-γ(p = 0.0105)和TNF-α(p < 0.0001)的水平显著高于健康对照组。最重要的是,最大抑制性Tregs群体中的TNFR2表达与WHO III型组织学类型、远处转移、进展性疾病状态和NPC患者的不良预后相关。因此,我们的研究暗示PB和TME Tregs的TNFR2表达可能是NPC患者的有用预测指标。版权所有 (Copyright) 2023 Elsevier Ltd. 保留所有权利。
TNFR2 is a surface marker of highly suppressive subset of CD4+ FoxP3+ regulatory T cells (Tregs) in humans and mice. This study examined the TNFR2 expression by Tregs of nasopharyngeal carcinoma (NPC) patients and healthy controls. The proliferation, migration, survival of TNFR2+ Tregs, and association with clinicopathological characteristics were assessed. The expression levels of selected cytokines were also determined. The results demonstrated that in both peripheral blood (PB) (10.45 ± 5.71%) and tumour microenvironment (TME) (54.38 ± 16.15%) of NPC patients, Tregs expressed TNFR2 at noticeably greater levels than conventional T cells (Tconvs) (3.91 ± 2.62%, p < 0.0001), akin to healthy controls. Expression of TNFR2 (1.06 ± 0.99%) was correlated better than CD25+ (0.40 ± 0.46%) and CD127-/low (1.00 ± 0.83% ) with FoxP3 expression in NPC PB (p = 0.0005). Though there was no significant association between TNFR2 expression with the functional capacity (proliferation, migration and survival) of Tregs (p > 0.05), the proportions of PB and TME TNFR2+ Tregs in NPC patients showed more proliferative, higher migration capacity, and better survival ability, as compared to those in healthy controls. Furthermore, TNFR2+ Tregs from NPC patients expressed significantly higher amounts of IL-6 (p = 0.0077), IL-10 (p = 0.0001), IFN-γ (p = 0.0105) and TNF-α (p < 0.0001) than those from healthy controls. Most significantly, TNFR2 expression in maximally suppressive Tregs population were linked to WHO Type III histological type, distant metastasis, progressive disease status, and poor prognosis for NPC patients. Hence, our research implies that TNFR2 expression by PB and TME Tregs may be a useful predictive indicator in NPC patients.Copyright © 2023 Elsevier Ltd. All rights reserved.