Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Endocrinology. 2020 Oct 1;161(10). doi: 10.1210/endocr/bqaa062.
The incidence of papillary thyroid cancer (PTC) with concomitant Hashimoto thyroiditis (HT) is increasing. Interleukin (IL)-10 is a cytokine previously reported to be elevated in this condition. Evidence from multiple human malignancies showed IL-10 participated in tumor immunity and exhibited therapeutic potential. The aim of this study is to investigate whether IL-10 interferes with tumor immunity in PTC with concomitant HT. Expression of IL-10 and major histocompatibility complex (MHC) class Ⅰ were compared with PTC tissues with or without concomitant HT. PTC cell lines K1 and TPC-1 were stimulated with IL-10 and analyzed for MHC class Ⅰ expression afterward. T-cell activation, production of IL-2 and interferon (IFN)-γ and programmed death-1 (PD-1) expression were assessed by coculture of donor peripheral blood lymphocytes (PBLs) with IL-10-pretreated PTC cells. Programmed death-ligand 1 (PD-L1) expression was measured in PTC tissues and IL-10-pretreated cells of K1 and TPC-1. Increased levels of IL-10 and MHC class Ⅰ were observed in PTC with concomitant HT. IL-10 stimulation increased MHC class Ⅰ expression of PTC cells in vitro. Coculture of PBLs with IL-10-pretreated PTC cells enhanced T-cell activation (% cluster of differentiation [CD]25+ of CD3+T cells) and increased IL-2 production along with decreased IFN-γ secretion and PD-1 expression. Reduced PD-L1 expression was seen in PTC + HT tissue samples and IL-10-stimulated PTC cell lines. Elevated IL-10 expression in PTC with concomitant HT restores MHC class Ⅰ expression and interferes with tumor immunity. The potential mechanism of IL-10 in tumor immunity needs further investigation.
甲状腺乳头状癌（PTC）合并桥本甲状腺炎（HT）的发病率正在增加。白细胞介素（IL）-10 是一种先前报道在这种情况下升高的细胞因子。来自多种人类恶性肿瘤的证据表明，IL-10 参与肿瘤免疫，并具有治疗潜力。本研究旨在探讨 IL-10 是否会干扰 PTC 合并 HT 中的肿瘤免疫。比较了伴有或不伴有 HT 的 PTC 组织中 IL-10 和主要组织相容性复合体（MHC）I 类的表达。用 IL-10 刺激 PTC 细胞系 K1 和 TPC-1，然后分析 MHC I 类的表达。通过用 IL-10 预处理的 PTC 细胞与供体外周血淋巴细胞（PBL）共培养，评估 T 细胞活化、IL-2 和干扰素（IFN）-γ的产生以及程序性死亡-1（PD-1）的表达。在 PTC 组织和 K1 和 TPC-1 的 IL-10 预处理细胞中测量程序性死亡配体 1（PD-L1）的表达。在 PTC 合并 HT 中观察到 IL-10 和 MHC I 类的水平升高。IL-10 刺激体外 PTC 细胞 MHC I 类表达增加。用 IL-10 预处理的 PTC 细胞与 PBL 共培养可增强 T 细胞活化（CD3+T 细胞中 CD25+的簇数百分比），增加 IL-2 的产生，同时减少 IFN-γ的分泌和 PD-1 的表达。在 PTC+HT 组织样本和 IL-10 刺激的 PTC 细胞系中观察到 PD-L1 表达降低。PTC 合并 HT 中升高的 IL-10 表达恢复 MHC I 类表达并干扰肿瘤免疫。IL-10 在肿瘤免疫中的潜在机制需要进一步研究。
