IL-17A increases MHC class I expression and promotes T cell activation in papillary thyroid cancer patients with coexistent Hashimoto's thyroiditis
IL-17A increases MHC class I expression and promotes T cell activation in papillary thyroid cancer patients with coexistent Hashimoto's thyroiditis
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IL-17A 增加甲状腺乳头状癌合并桥本甲状腺炎患者 MHC I 类表达并促进 T 细胞活化
DOI：
10.1186/s13000-019-0832-2
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发表时间：
2019-06-04
影响因子：
2.6
通讯作者：
Ji, Qing-Hai
中科院分区：
文献类型：
--
作者：
Han, Li-Tao;Hu, Jia-Qian;Ji, Qing-Hai
研究背景甲状腺乳头状癌(PTC)与桥本甲状腺炎(HT)并存的发病率呈上升趋势。甲状旁腺激素对PTC预后的影响及其可能的机制仍存在争议。白介素17A(IL-17A)参与了多种自身免疫性疾病和癌症的发病机制。本研究的目的是探讨IL-17A在PTC伴发甲状旁腺癌中的作用，评价其在肿瘤抗原性中的变化。用IL-17A刺激PTC细胞株K1和TPC-1，检测MHC-I类分子的表达。将供者外周血淋巴细胞(PBL)与经IL-17A处理的PTC细胞共培养，检测CD8(+)T细胞的活化、IL-2和干扰素-γ(干扰素-γ)的产生以及淋巴细胞上程序性死亡-1(PD-1)的表达。IL-17A体外刺激PTC细胞可有效增加MHC-I类分子的表达。经IL-17A处理的PTC细胞与PBL共培养后，CD3(+)T细胞的活性(%CD25+)增强，IL-2的产生增加，同时淋巴细胞的干扰素分泌和PD-1表达降低。结论甲状腺乳头状癌合并桥本甲状腺炎患者存在MHC-I类分子的高表达，可能与IL-17A的分泌有关。IL-17A在体外可增强T细胞的活性，并可能在PTC免疫治疗中提供应用前景。
BackgroundThe incidence of coexisting papillary thyroid cancer (PTC) and Hashimoto's thyroiditis (HT) is increasing. The impact of HT on PTC prognosis and its possible mechanism remains controversial. Interleukin-17A (IL-17A) has been reported to participate in the pathogenesis of multiple autoimmune diseases and cancers. The aim of this study is to investigate the role of IL-17A in PTC with coexistent HT and evaluate the changes in tumor antigenicity.MethodsExpression of IL-17A and major histocompatibility complex (MHC) class I molecules were compared on PTC tissue samples with or without HT. PTC cell lines K1 and TPC-1 were stimulated with IL-17A and analyzed for MHC class I expression afterwards. Cluster of differentiation (CD) 8(+)T cell activation, production of Interleukin-2 (IL-2) and Interferon-gamma (IFN-) as well as the programmed death-1 (PD-1) expression on lymphocytes were assessed by coculture of donor peripheral blood lymphocytes (PBLs) with IL-17A pretreated PTC cells.ResultsElevated IL-17A and MHC class I expression were observed in PTC tissue samples with coexistent HT. Stimulation of PTC cells with IL-17A effectively increased MHC class I expression in vitro. Coculture of PBLs with IL-17A pretreated PTC cells resulted in enhanced T cell activation (%CD25(+) of CD3(+)T cells) and increased IL-2 production along with decreased IFN- secretion and PD-1 expression of the lymphocytes.ConclusionsPapillary thyroid cancer with coexisting Hashimoto's thyroiditis presents elevated MHC class I expression, which may be the result of IL-17A secretion. T cell activation is enhanced in vitro by IL-17A and may provide future utility in PTC immunotherapy.