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IL-17A increases MHC class I expression and promotes T cell activation in papillary thyroid cancer patients with coexistent Hashimoto's thyroiditis.

ABSTRACT: BACKGROUND:The 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. METHODS:Expression 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. RESULTS:Elevated 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. CONCLUSIONS:Papillary 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.

SUBMITTER: Han LT

PROVIDER: S-EPMC6547553 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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IL-17A increases MHC class I expression and promotes T cell activation in papillary thyroid cancer patients with coexistent Hashimoto's thyroiditis.

Han Li-Tao LT Hu Jia-Qian JQ Ma Ben B Wen Duo D Zhang Ting-Ting TT Lu Zhong-Wu ZW Wei Wen-Jun WJ Wang Yu-Long YL Wang Yu Y Liao Tian T Ji Qing-Hai QH

Diagnostic pathology 20190604 1

<h4>Background</h4>The 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.<h4>Methods</h4>Expression of IL-17 ...[more]

PMID: 31159823

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Project description:BackgroundHashimoto's thyroiditis (HT) is the most prevalent inflammatory disorder of the thyroid gland. Current studies have reported the coexistence rate between HT and papillary thyroid carcinoma (PTC) is quite high. The objective of this study was to evaluate the impact of HT on the predictive factors of central compartment lymph node metastasis (CLNM) in PTC.MethodsA retrospective investigation was performed on PTC patients. They were subclassified into HT and non-HT groups. The results of preoperative neck ultrasound (US) examinations were reviewed. The clinical characteristics and the predictive value for CLNM were explored and compared between the two groups.ResultsA total of 756 patients were included in this study. There were more female patients (86.1%) in the PTC coexistent with the HT group than non-HT group. The patients with HT group had higher preoperative serum level of TSH. There was statistically significant difference between the HT patients and non-HT patients in nodular vascularization. Univariate and multivariate analyses showed that male, age ≤45 years old, tumor diameter >1 cm, and presence of suspicious central compartment lymph node on US, irregular nodular shape, multifocal carcinoma were independent predictive factors of CLNM in PTC patients. It was showed that male, age ≤45 years old, tumor diameter >1 cm, multifocality, and presence of suspicious central lymph node on US were risk factors for CLNM in non-HT patients. Only tumor diameter >1 cm and presence of suspicious central lymph node on US were independently correlated with CLNM in HT patients. The sensitivity of the multivariate model was 63.5%, and specificity was 88.9% for prediction CLNM in HT patients. For non-HT patients, the AUC was 80.6%, the sensitivity of the multivariate model was 64.5%, and specificity was 85.2.ConclusionPTC combined with HT is more common in women, and TSH level in HT group is higher than that in patients with PTC alone. Regardless of that HT is not a related risk factor of CLNM in PTC, our result suggested that different predictive systems should be used for HT and non-HT patients respectively to have a more accurate evaluation of CLNM in clinic.

Project description:ObjectiveThe incidence of papillary thyroid cancer (PTC) concomitant with Hashimoto's thyroiditis (HT) is gradually increasing over the past decades. This study aims to identify differentially expressed lncRNAs between tumor tissues of PTC with or without HT and further to confer a better understanding of lncRNA-based competing endogenous RNA (ceRNA) network in PTC with HT.MethodsGSE138198 containing tissue mRNA data and GSE192560 containing lncRNA data were utilized to perform differentially expression analysis. The ceRNA network was constructed based on miRNA-mRNA interactions merging with lncRNA-microRNA interactions. Functional enrichment analysis and protein-protein interaction (PPI) analysis were performed. The mRNA levels of core genes in the PPI analysis in tumor tissues collected from 112 PTC patients including 35 cases coexistent with HT were determined by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsA total of 57 genes and 40 lncRNAs, with value of |log2 fold change (FC)|≥ 1 and the adjusted P-value < 0.05, were deemed as differentially expressed genes and lncRNAs between PTC with and without HT. The pathways most significantly enriched by differentially expressed genes between PTC with and without HT were viral protein interaction with cytokine and cytokine receptor and cytokine-cytokine receptor interaction. CXCL10, CXCL9, CCL5, FCGR3A, and CCR2 owned degree values not less than 10 were deemed as core genes differentially expressed between PTC with and without HT. A total of 76 pairs of lncRNA-miRNA-mRNA ceRNA were obtained. Results of qRT-PCR partially demonstrated the bioinformatics results that the mRNA levels of CXCL10, CXCL9, CCL5, and CCR2 were remarkably elevated in tumor tissues collected from PTC patients coexistent with HT than those without HT (P < 0.001).ConclusionOur study offers a better understanding of the lncRNA-related ceRNA network involved in PTC with HT, providing novel key genes associated with PTC coexistent with HT.

Dataset Information

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 increases MHC class I expression and promotes T cell activation in papillary thyroid cancer patients with coexistent Hashimoto's thyroiditis.

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