Abstract
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-γ) 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-γ 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.
Highlights
The incidence of coexisting papillary thyroid cancer (PTC) and Hashimoto’s thyroiditis (HT) is increasing
In the current study, we identified an elevated expression of IL-17A in PTC with coexisting HT
Administration of IL-17A could effectively induce major histocompatibility complex (MHC) class I expression in K1 and TPC-1 cells in vitro, which led to increased T cell activation and IL-2 production by Peripheral blood lymphocytes (PBL) cocultured with IL-17A pretreated PTC cell lines
Summary
The incidence of coexisting papillary thyroid cancer (PTC) and Hashimoto’s thyroiditis (HT) is increasing. Interleukin-17A (IL-17A) has been reported to participate in the pathogenesis of multiple autoimmune diseases and cancers. Most of these studies argued patients with HT are more likely to have favorable prognosis, including one study completed at our institute [2, 5, 6]. Multiple cytokines are involved in HT pathogenesis and they can affect the course of the disease [9]. Cytokines are decisive regarding tumor growth and metastasis in various cancers, including PTC [10, 11]. Of special interest is interleukin 17A (IL-17A), whose expression is reported to be elevated in autoimmune diseases [12, 13]
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