Metastatic thyroid cancers are more difficult to treat and have a significantly worse prognosis than localized thyroid cancers. Previous studies have shown that follicular helper T cells (Tfh) may participate in antitumor immune responses. Here, we investigated the characteristics of Tfh cells in patients with differentiated thyroid cancer (DTC) at various severities, including patients with localized disease, cervical metastasis, and distant metastasis. In circulating CD4 T cells, the proportion of CD4⁺CXCR5⁺ Tfh‐like cells was significantly higher in patients with distant metastasis than in healthy controls, patients with local disease, and patients with cervical metastasis. Also, the expression of Tfh cell‐associated surface molecules, such as PD‐1, ICOS, and BTLA, tended to be higher in patients with cervical and distant metastasis than in healthy controls. However, the expression of secreted molecules, such as IL‐10, IL‐21, and CXCL13, was significantly lower in patients with distant metastasis than in healthy controls and patients with local disease. Additionally, circulating Tfh‐like cells from patients with distant metastasis were less capable of supporting B‐cell growth and IgM secretion. We also examined the CD4⁺CXCR5⁺ Tfh‐like cells in tumor samples. Tumor‐infiltrating Tfh‐like cells were highly enriched in the pulmonary metastasis compared to the local tumor and the cervical metastasis. However, tumor‐infiltrating Tfh‐like cells from pulmonary metastasis displayed higher PD‐1, TIM‐3, and lower IL‐21 expression than those from the local tumor. Together, this study identified that the metastasis of DTC patients was associated with an overabundance of defective Tfh cells.

中文翻译：

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甲状腺癌转移与卵泡辅助性T细胞缺陷过多有关。

转移性甲状腺癌比局限性甲状腺癌更难治疗，预后也明显较差。先前的研究表明，卵泡辅助性T细胞（Tfh）可能参与抗肿瘤免疫反应。在这里，我们调查了各种严重程度的分化型甲状腺癌（DTC）患者的Tfh细胞特征，包括局部疾病，宫颈转移和远处转移的患者。在循环的CD4 T细胞中，CD4 ⁺ CXCR5 ⁺远处转移患者的Tfh样细胞明显高于健康对照组，局部疾病患者和宫颈转移患者。而且，Tfh细胞相关表面分子（例如PD-1，ICOS和BTLA）的表达在宫颈和远处转移的患者中比在健康对照组中更高。但是，远处转移患者的分泌分子如IL-10，IL-21和CXCL13的表达明显低于健康对照者和局部疾病患者。此外，来自远处转移患者的循环Tfh样细胞支持B细胞生长和IgM分泌的能力较弱。我们还检查了CD4 ⁺ CXCR5 ⁺肿瘤样本中的Tfh样细胞。与局部肿瘤和宫颈转移相比，浸润肿瘤的Tfh样细胞在肺转移中高度富集。然而，与肺部转移相比，肺转移瘤浸润的Tfh样细胞显示出更高的PD-1，TIM-3和更低的IL-21表达。总之，这项研究确定了DTC患者的转移与缺陷性Tfh细胞过多有关。