甲状腺乳头状癌患者外周血Treg细胞和NK细胞检测及其临床意义  

Detection of regulatory T cells and NK cells in peripheral blood of patients with papillary thyroid carcinoma and its clinical significance

作　　者：孙鑫 刘业海[3] 郑美娟[2] Sun Xin;Liu Yehai;Zheng Meijuan(Department of Immunology,School of Basic Medical Sciences Anhui Medical University,Hefei 230032,China;Department of Clinical Laboratory,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,China;Department of Otolaryngology,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,China)

机构地区：[1]安徽医科大学基础医学院免疫学教研室,合肥230032 [2]安徽医科大学第一附属医院检验科,合肥230022 [3]安徽医科大学第一附属医院耳鼻咽喉头颈外科,合肥230022

出　　处：《临床与实验病理学杂志》2025年第1期23-31,共9页Chinese Journal of Clinical and Experimental Pathology

基　　金：国家自然科学基金重大研究计划(92269109);安徽省自然科学基金优青项目(2208085Y29)。

摘　　要：目的 探讨甲状腺乳头状癌(papillary thyroid carcinoma, PTC)患者外周血免疫抑制性调节性T细胞(Treg细胞)和自然杀伤(natural killer, NK)细胞与肿瘤发生、发展的关系。方法 对结节性甲状腺肿患者和PTC患者的病理组织切片进行HE染色,评估免疫细胞的浸润情况;流式细胞术检测健康对照者(healthy control, HC)和PTC患者外周血Treg细胞和NK细胞的百分比和绝对计数,对比Treg细胞的表型(ICOS、PD-1、Lag3)和IL-10分泌能力;分析NK细胞效应功能(TNF-α、IFN-γ、Granzyme B、Perforin)的改变;流式微球阵列检测血清中细胞因子IL-10的浓度,分析Treg细胞和NK细胞变化及其相关性。结果 PTC组织中炎细胞浸润水平高于结节性甲状腺肿组织;与HC相比,PTC患者外周血中Treg细胞的百分比[(6.86±3.10)%]和绝对计数[(4.97±2.82)×10^(6)个/mL]明显增加,且分泌IL-10的能力[(7.18±3.57)%]增强,并与肿瘤的淋巴结转移和脉管侵犯有关;相反,PTC患者外周血中NK细胞百分比[(16.56±8.44)%]和绝对计数[(3.29±3.12)×10^(6)个/mL]降低,效应功能下降;PTC患者外周血中NK细胞与Treg细胞的比值(2.49±1.60)下降,且两者之间具有显著的负相关(P=0.04,r=-0.625);PTC患者血清中IL-10的浓度升高[(1.30±1.09) pg/mL],并与肿瘤的大小和淋巴结转移有关;PTC患者经1,25-(OH)_(2)-D_(3)治疗后,外周血中CD4^(+)CD25^(+)CD127^(low)Treg细胞的百分比[(7.01±2.13)%]和绝对计数[(4.27±1.62)×10^(6)个/mL]及血清中细胞因子IL-10的浓度[(1.27±0.09) pg/mL]明显下降,而循环NK细胞的百分比[(20.6±6.72)%]和绝对计数[(5.63±2.93)×10^(6)个/mL]显著增加。结论 PTC患者呈明显的免疫抑制状态,Treg细胞与NK细胞数量和功能异常与PTC的发生发展及预后有关,提示其在肿瘤免疫治疗中的重要价值。Purpose To explore the relationship between regulatory T cells(Treg cells)and natural killer(NK)cells with tumor occurrence and development in papillary thyroid carcinoma(PTC).Methods Hematoxylin and eosin(HE)staining was performed on pathological tissue sections from patients with nodular goiter and PTC to evaluate immune cell infiltration.Flow cytometry was used to detect the percentage and absolute count of Treg cells and NK cells in peripheral blood from healthy controls(HCs)and PTC patients.Treg cells phenotypes(ICOS、PD-1、Lag3)and their IL-10 secretion ability were analayzed,along with functional molecules(TNF-α、IFN-γ、Granzyme B、Perforin)expressed by NK cells.A cytometric bead array was used to measure serum cytokine IL-10 concentration.Changes in Treg and NK cells and their correlations were analyzed.Results Immune cell infiltration in PTC tissues is higher than in nodular goiter tissue.Compared with healthy controls,PTC patients exhibited a significant increase in the percentage[(6.86±3.10)%]and absolute count[(4.97±2.82×10^(6) cells/mL)]of circulating Treg cells,with an enhanced IL-10 secretion capacity[(7.18±3.57)%],which is related to lymph node metastasis and vascular invasion.Conversely,NK cell percentage[(16.56±8.44)%]and absolute count[(3.29±3.12×10^(6) cells/mL)]were reduced,with impaired effector functions.The NK-to-Treg cell ratio(2.49±1.60)significantly declined,and a negative correlation was observed between the percentage of the two groups cell types(P=0.04,r=-0.625).Serum IL-10 levels in PTC patients were elevated[(1.30±1.09)pg/mL],correlating with tumor size and lymph node metastasis.After treatment with 1,25-(OH)_(2)-D_(3),PTC patients showed a reduction in the percentage[(7.01±2.13)%]and absolute count(4.27±1.62×10^(6) cells/mL)of circulating CD4^(+)CD25^(+)CD127 low Treg cells,and a decrease in serum cytokine IL-10 levels[(1.27±0.09)pg/mL].Circulating NK cells percentages[(20.6±6.72)%]and absolute counts[(5.63±2.93)×10^(6) cells/mL]partially recovered.Conclusio

关 键 词：甲状腺肿瘤 TREG细胞 NK细胞 IL-10 1 25-(OH)_2-D_3 

分 类 号：R736.1[医药卫生—肿瘤]