Increased frequency and suppressive activity of CD127low/- regulatory T cells in the peripheral circulation of patients with head and neck squamous cell carcinoma are associated with advanced stage and nodal involvement
Increased frequency and suppressive activity of CD127low/- regulatory T cells in the peripheral circulation of patients with head and neck squamous cell carcinoma are associated with advanced stage and nodal involvement
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DOI：
10.1111/imm.12144
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发表时间：
2013-11-01
期刊：
影响因子：
6.4
通讯作者：
Green, Victoria L.
中科院分区：
文献类型：
--
作者：
Drennan, Samantha;Stafford, Nicholas D.;Green, Victoria L.
调节性T （Treg）细胞的存在被认为是头颈部鳞状细胞癌（HNSCC）成功逃避免疫系统的重要机制。采用多色流式细胞术，根据不同CD25表达水平（CD25（间）和CD25（高））分离的两种CD4(+)CD127（低/-）Treg细胞群的频率和功能容量，从新发HNSCC患者的外周循环中评估其临床病理特征和健康对照。HNSCC患者和健康对照组之间循环Treg细胞的频率相似，发生于不同亚位点（喉部与口咽）的HNSCC患者之间循环Treg细胞的频率相似。然而，与早期肿瘤患者（P=003）和无淋巴结受累患者（P=003）相比，晚期肿瘤患者和淋巴结受累患者的CD4(+)CD25（高）CD127（低/-）Treg细胞水平分别显著升高。与健康对照组（P=004）或无淋巴结累及患者（P=004）相比，来自整个HNSCC患者队列和肿瘤转移到淋巴结的患者的CD4(+)CD25（高）CD127（低/-）Treg细胞也显示出更显著地抑制效应T细胞的增殖。此外，CD4(+)CD25（间）CD127（低/-）Treg细胞对效应t细胞群(CD4(+)CD25(-)CD127（-/+）和CD4(+)CD25（+)CD127(+)）增殖的抑制活性始终高于CD4(+)CD25（高）CD127（低/-）Treg细胞。经CD127（低/-）表型鉴定的外周Treg细胞已被证明受HNSCC患者肿瘤分期和/或淋巴结状态的影响；这表明它在肿瘤进展中的作用可能被未来的免疫疗法所控制。
The presence of regulatory T (Treg) cells is thought to be an important mechanism by which head and neck squamous cell carcinoma (HNSCC) successfully evades the immune system. Using multicolour flow cytometry, the frequency and functional capacity of two CD4(+)CD127(low/-) Treg cell populations, separated on the basis of different levels of CD25 expression (CD25(inter) and CD25(high)), from the peripheral circulation of newly presenting HNSCC patients were assessed with regard to clinicopathological features and healthy controls. The frequency of circulating Treg cells was similar between HNSCC patients and healthy controls, and for patients with HNSCC developing from different subsites (laryngeal compared with oropharyngeal). However, patients with advanced stage tumours and those with nodal involvement had significantly elevated levels of CD4(+)CD25(high)CD127(low/-) Treg cells compared with patients who had early stage tumours (P=003) and those without nodal involvement (P=003), respectively. CD4(+)CD25(high)CD127(low/-) Treg cells from the entire HNSCC patient cohort and from patients whose tumours had metastasized to the lymph nodes were also shown to suppress the proliferation of effector T cells significantly more, compared with those from healthy controls (P=004) or patients with no nodal involvement (P=004). Additionally, CD4(+)CD25(inter)CD127(low/-) Treg cells consistently induced greater suppressive activity than CD4(+)CD25(high)CD127(low/-) Treg cells on the proliferation of the effector T-cell populations (CD4(+)CD25(-)CD127(-/+) and CD4(+)CD25(+)CD127(+)). Peripheral Treg cells, identified by the CD127(low/-) phenotype, have been shown to be influenced by a patient's tumour stage and/or nodal status in HNSCC; suggesting a role in tumour progression that could be manipulated by future immunotherapy.