T cell exhaustion is associated with the risk of papillary thyroid carcinoma and can be a predictive and sensitive biomarker for diagnosis

Abstract

Background The incidence of papillary thyroid carcinoma (PTC) has been steadily increasing over the past decades. Hashimoto’s thyroiditis (HT) is the most common autoimmune disease, and is related to the pathogenesis of PTC. Programmed cell death protein-1 (PD-1) is currently used for the treatment of PTC, but there are very few studies on the clinical value of PD-1 in the diagnosis and targeted therapy of PTC. Methods The expressions of PD-1 in the peripheral blood of 139 patients with PTC (PTC group), 48 patients with thyroid nodules (TN group) and 63 healthy subjects (HP group) were detected by flow cytometry. The expressions of plasma T3, T4, FT3, FT4, TSH, TGAb and TPO were detected by chemiluminescence immunoassay. T cell subsets, thyroid function indexes and PD-1 were also detected. Results The expressions of FT3, TGAb, CD3+PD-1+, CD3+CD4+PD-1+ and CD3+CD8+PD-1+ in PTC and TN were significantly higher than that in the HP group. Moreover, CD3+PD-1+, CD3+CD4+PD-1+ and CD3+CD8+PD-1+ expressions had significant differences between the PTC group and the TN group. In addition, the expressions of TGAb, TPO, CD3+PD-1+, CD3+CD4+PD-1+ and CD3+CD8+PD-1+ in PTC combined with HT (PCH group) were significantly higher than that in the PTC group. PD-1 showed a significant correlation with PTC lymph node metastasis. CD3+PD-1+ and CD3+CD4+PD-1+ expressions were higher in N1 stage than in N0 stage. Conclusions The present study showed that T cell exhaustion might act as a biomarker for the differential diagnosis of PTC and TN. The combination of PD-1, TGAb and TPO might be used as an early warning biomarker for the progression of HT to PTC. Targeting the PD-1 pathway could be a new approach to treat PTC and prevent malignant transformation from HT to PCH in the future.