Mechanisms of the Impact of Hashimoto Thyroiditis on Papillary Thyroid Carcinoma Progression: Relationship with the Tumor Immune Microenvironment.

Abstract

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.

• Authors: Oksana Sulaieva, Olena Chernenko, Oleksiy Selesnov, Oleksandr Nechay, Oleksandr Maievskyi, Tetyana Falalyeyeva, Nazarii Kobyliak, Olena Tsyryuk, Yurii Penchuk, Dmytro Shapochka
• Journal: Endocrinology and metabolism (Seoul, Korea) (Endocrinol Metab (Seoul)) Vol. 35 Issue 2 Pg. 443-455 (06 2020) ISSN: 2093-5978 [Electronic] Korea (South)
• PMID: 32615729 (Publication Type: Journal Article)

Topics

• Adult
• Carcinoma, Papillary (immunology, pathology)
• Disease Progression
• Female
• Follow-Up Studies
• Hashimoto Disease (physiopathology)
• Humans
• Male
• Middle Aged
• Pilot Projects
• Prognosis
• T-Lymphocytes, Regulatory (immunology)
• Thyroid Neoplasms (immunology, pathology)
• Tumor Microenvironment (immunology)
• Young Adult