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IL-10 恢复 MHC Ⅰ类分子表达并干扰桥本甲状腺炎合并甲状腺乳头状癌的免疫。

IL-10 Restores MHC Class I Expression and Interferes With Immunity in Papillary Thyroid Cancer With Hashimoto Thyroiditis.

机构信息

Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

Endocrinology. 2020 Oct 1;161(10). doi: 10.1210/endocr/bqaa062.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1ef/7469947/7abd19ec058b/bqaa062f0001.jpg

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