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KMID : 1141520200350020443
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Endocrinology and Metabolism
2020 Volume.35 No. 2 p.443 ~ p.455
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Mechanisms of the Impact of Hashimoto Thyroiditis on Papillary Thyroid Carcinoma Progression: Relationship with the Tumor Immune Microenvironment
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Sulaieva Oksana
Chernenko Olena
Selesnov Oleksiy
Nechay Oleksandr
Maievskyi Oleksandr
Falalyeyeva Tetyana
Kobyliak Nazarii
Tsyryuk Olena
Penchuk Yurii
Shapochka Dmytro
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Abstract
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Background: The relationship between Hashimoto thyroiditis (HT) and papillary thyroid carcinoma (PTC) remains uncertain. We assessed the impact of HT on the tumor immune microenvironment (TIME) in PTC.
Methods: Thirty patients with PTC (group 1) and 30 patients with PTC and HT (group 2) were enrolled in this pilot study. The distribution and number of CD8+ lymphocytes, plasma cells (CD138+), regulatory T cells (forkhead box P3 [FOXP3+)], mast cell tryptase (MCT+), and M2 macrophages (CD163+) were evaluated. To test the hypothesis that HT impacts PTC development via signal transducer and activator of transcription 6 (STAT6) activation and M2 macrophage polarization, we investigated STAT6 expression in tumor and stromal cells. We also evaluated vascular endothelial growth factor (VEGF) expression by lymph node metastasis (LNM) status.
Results: TIME showed significant between-group differences. Group 1 patients demonstrated immune desert or immune-excluded immunophenotypes, while an inflamed phenotype with more CD8+ cells (P<0.001) predominated in group 2. Immune-excluded TIME was associated with the highest LNM rate. In PTC, LNM was associated with more numerous CD163+ cells. Moreover, LNM in group 1 was associated with increased numbers of mast cells peritumorally and FOXP3+ cells intratumorally and peritumorally. Group 2 demonstrated higher STAT6 but not higher VEGF expression in tumor cells. High VEGF expression was associated with LNM regardless of HT status.
Conclusion: Concomitant HT impacted PTC signaling via STAT6 and TIME by increasing the number of CD8+ cells. LNM is associated with increases in CD163+ cells and VEGF expression in PTC, whereas HT affected LNM through different mechanisms.
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KEYWORD
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Thyroid cancer, papillary, Hashimoto disease, Metastasis, T-lymphocytes, Macrophages
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