Serum soluble immune checkpoint levels predict cervical lymph node metastasis of differentiated thyroid carcinoma patients

BACKGROUND: Cervical lymph node metastasis (CLNM) is common in patients with differentiated thyroid carcinoma (DTC); however, the efficiency to distinguish CLNM before surgery is limited. T cell exhaustion, characterized by the overexpression of immune checkpoints, plays a critical role in the immune evasion of tumors. The aim of this study is to analyze the association between serum levels of soluble immune checkpoints (sICs) and CLNM in DTC patients. METHODS: Levels of sICs in serum of 71 DTC patients and 56 healthy volunteers were analyzed by ELISA. Peripheral blood mononuclear cells and cervical lymph nodes of DTC patients were isolated and their expression of sICs were analyzed. Lymphocytes in cervical lymph nodes were analyzed for immune checkpoints expression and transcription of exhaustion‐associated factors. 30 out of 71 DTC patients were followed up from 3 to 9 months after the operation, and postoperative sTIM‐3 were analyzed. RESULTS: Four sICs, including LAG‐3, PD‐1, PD‐L1, and TIM‐3, were increased in DTC patients. All four sICs exhibited higher sensitivity at discriminating CLNM than cervical ultrasound. In the patient‐matched comparison, higher sTIM‐3 levels were observed in tumor‐involved lymph nodes (TILNs) than in normal lymph nodes (nLNs). T lymphocytes in TILNs had higher TIM‐3 surface expression and increased secretion of sTIM‐3 than those in patient‐matched nLNs. Finally, postoperative serum sTIM‐3 levels were decreased in DTC patients with CLNM compared to their preoperative levels. CONCLUSION: Serum levels of sICs, especially sTIM‐3, could help to predict CLNM and provide evidence for surgical decision‐making in DTC.