The Immunologic Impact of Hashimotos Thyroiditis on Papillary Thyroid Carcinoma: A Systematic Research

Abstract

Background: The immunological relationship and the molecular mechanisms underlying the co-occurrence of papillary thyroid carcinoma (PTC) and Hashimotos thyroiditis (HT) are yet to be known. This study aimed to explore the immunological and clinical association between papillary thyroid carcinoma (PTC) and Hashimotos thyroiditis (HT). Method: 680 PTC patients were evaluated for clinicopathological factors and serum thyroid-function level. Among 680 PTC patients, 129 PTC patients with or without HT were investigated the immune-related cytokine levels such as Interleukin, tumor necrosis factor and immune cell percentages (cluster of differentiation (CD)4, CD8, CD3) in the serum using the immunofluorescence-flow cytometry technique. We explored the characteristics of tumor immune microenvironment and the levels of immune cell infiltration of CD4, CD8, CD3, CD20 in tissues using Immunohistochemistry. Results: It was found that the patients with co-existing PTC and HT (PTC+HT) had lower levels of Interleukin-2 (IL-2) (p = 0.023) and Interferon-γ (IFN-γ) (p = 0.003) than those with PTC alone. There was no significant difference in the proportions of CD4, CD8, and CD3 cells in the two groups (p > 0.05). Additionally, the proportions of CD4 and CD3 cells were significantly lower in the PTC+HT group than those with HT alone (p < 0.05). Furthermore, the PTC+HT group had lower lymph node metastasis rates (p = 0.001) and showed no significant difference in the stratification of postoperative recurrence risk (p < 0.05) than those with PTC alone. Moreover, it was observed that the patients with HT had higher levels of CD4+ and CD3+ cell infiltration in their intact thyroid tissues than those with PTC+HT. The level of CD8+ cells was significantly higher in the PTC+HT group of patients than those with PTC alone. However, the level of CD4+ cells was found to be lower in the PTC+HT group of patients. The PTC+HT group of patients with negative lymph node status had more prominent CD4+ T cells intratumoral infiltration than those with positive lymph node metastasis (LNM) (p < 0.05). Moreover, PTC+HT and PTC patients with LNM+ status had lower CD8+ T cell infiltration levels than those with LNM-status (p < 0.05). Conclusion: HT does not attenuate the aggressive factor of lymph node metastasis in PTC patients. Patients with PTC+HT may have different anti-tumor immune mechanisms impacting lymph node metastasis and lower levels of CD4+Th1 cellular immunity than patients with PTC.