Thyroid cancer is the most common endocrine malignancy, with an increasing global incidence. Despite advances in conventional treatments, such as surgery, radioactive iodine therapy, and TSH suppression, the management of advanced and aggressive forms, such as anaplastic thyroid carcinoma and refractory differentiated thyroid carcinoma, remains a challenge. Immunotherapy has emerged as a promising approach, with immune checkpoint inhibitors (ICIs) like PD‐1/PD‐L1 and B7‐H3 showing potential in enhancing antitumor immunity. Additionally, immune cells such as CD4+, CD8+, and M2 macrophages are key players in the tumor microenvironment, influencing treatment responses and serving as prognostic biomarkers. Combining ICIs with targeted therapies or adoptive cell therapies is being explored to overcome resistance and improve efficacy. However, challenges such as tumor heterogeneity and immune evasion mechanisms persist.

Autoimmune thyroiditis (AIT) is a common endocrine disease which causes a significantly increased risk of miscarriage. Our recent study has shown that the increased ENO1 autoantibody (ENO1Ab) expression in an experimental AIT mouse model was induced by thyroglobulin (Tg) immunization only. In this study, we explored the potential roles of ENO1Ab in miscarriage occurrence among AIT women, and the specific epitopes of ENO1 targeted by ENO1Ab. A total of 432 euthyroid pregnant participants were selected from the project of Subclinical Hypothyroid during Early Pregnancy, including 48 women with AIT and miscarriage, 96 with miscarriage but no AIT, 96 with AIT but no miscarriage, and 192 without either AIT or miscarriage. The enzyme-linked immunosorbent assay was used to determine the serum levels of total IgG against ENO1 and 18 predicted antigen epitopes of ENO1. The results showed that women with AIT and miscarriage had the highest serum levels of ENO1Ab compared to the other groups. Logistic regression analysis showed that the serum ENO1Ab was an independent risk factor for miscarriage, especially among AIT females. The serum level of total IgG against the predicted epitope peptide 6 (i.e., P6 and aa168-183) of ENO1 was significantly increased in women with AIT and miscarriage when compared with those of both the AIT non-miscarriage group and non-AIT miscarriage group. This pilot study suggests that serum ENO1Ab may have a fair predictive value for AIT-related miscarriage, and the autoantibody specific to P6 epitope may especially be more specifically related to this disorder.