Cytokine production of papillary thyroid carcinoma coexisting with Hashimoto's thyroiditis

Abstract

In the tumor microenvironment coexisting with Hashimoto's thyroiditis (HT), cytokines secreted by the tumor cells, stroma cells, or immune cells play a critical role in the regulation of tumor growth, invasion, and metastasis. The present study aims to understand cytokine production from cancerous tissues (CT), para-cancerous tissues (PT), and serum in patients with papillary thyroid carcinoma (PTC) with or without accompanying HT. Using a multiplexed human cytokine assay, we found that nine cytokines, including Interleukin-1alpha (IL-1α), Interleukin-1beta (IL-1β), Interleukin-12p70 (IL-12p70), Interleukin-8 (IL-8), Interferon-inducible protein-10 (IP-10), Monocyte chemoattractant protein-1 (MCP-1), Macrophage inflammatory protein-1alpha (MIP-1α), Macrophage inflammatory protein-1beta (MIP-1β), and soluble E-selectin (sE-Selectin), showed significantly higher expression in para-cancerous tissues of HT⁺PTC compared with HT^-PTC (P<0.05). In addition, H&E staining showed immune cell infiltration in PT but not in CT. Moreover para-cancerous tissues of HT⁺PTC patients produced more Interferon-alpha (IFN-α) (P=0.048) and Interferon-gamma (IFN-γ) (P=0.004) compared with cancerous tissues, and production of Intercellular cell adhesion molecule-1 (ICAM-1) was significantly higher in CT than PT both in HT⁺PTC (P=0.001) and HT^-PTC (P=0.012) patients. To conclude, autoimmune HT was found to affect the cytokine profiles in patients with PTC by stimulating secretion of Th1-type cytokines and chemokines, but further studies are needed to determine the significance of these findings and to reveal the exact mechanism of the interactions between chemokines and cytokines in the pathogenesis of HT and PTC.

Keywords: Hashimoto’s thyroiditis; chemokine; cytokine; papillary thyroid carcinoma.

Figure 1

Representative hematoxylin and eosin-stained sections of cancerous tissues and para-cancerous tissues (40× magnification). A. Cancerous tissue (HT⁺PTC): few immune cells; B. Para-cancerous tissue (HT⁺PTC): immune cells infiltrated into para-cancerous tissues with distinct lymphoid follicular (LF) growth; C. Cancerous tissue (HT^-PTC): very few infiltrated immune cells; D. Para-cancerous tissue (HT^-PTC): almost no infiltrated immune cells.

Figure 2

Higher expression levels of (A) IL-1α, (B) IL-1β, (C) IL-12p70, (D) IL-8, (E) IP-10, (F) MCP-1, (G) MIP-1α, (H) MIP-1β and (I) sE-Selectin in para-cancerous tissues of PTC patients with HT compared with those without HT (t-test, *P<0.05, **P≤0.01, ***P≤0.001).

Figure 3

Expression levels of ICAM-1 (A), IFN-α (B), and IFN-γ (C) in HT⁺PTC and HT^-PTC groups (t-test, *P<0.05, **P≤0.01, ***P≤0.001).