Qian Guangfang, Wu Min, Zhao Yuanyuan, Li Qing, Zhang Mimi, Cai Chen, Tong Danian
Department of Endocrinology, Jinan Zhangqiu District Hospital of TCM, Jinan, Shandong, China.
Department of Special Clinic, Changhai Hospital, Shanghai, China.
APMIS. 2020 Aug;128(8):487-496. doi: 10.1111/apm.13062.
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.
转移性甲状腺癌比局限性甲状腺癌更难治疗，预后明显更差。先前的研究表明，滤泡辅助性T细胞（Tfh）可能参与抗肿瘤免疫反应。在此，我们调查了不同严重程度的分化型甲状腺癌（DTC）患者中Tfh细胞的特征，包括局限性疾病患者、颈部转移患者和远处转移患者。在循环CD4 T细胞中，远处转移患者的CD4 CXCR5 Tfh样细胞比例显著高于健康对照、局限性疾病患者和颈部转移患者。此外，Tfh细胞相关表面分子如PD-1、ICOS和BTLA的表达在颈部和远处转移患者中往往高于健康对照。然而，远处转移患者中IL-10、IL-21和CXCL13等分泌分子的表达显著低于健康对照和局限性疾病患者。此外，远处转移患者的循环Tfh样细胞支持B细胞生长和IgM分泌的能力较低。我们还检查了肿瘤样本中的CD4 CXCR5 Tfh样细胞。与局部肿瘤和颈部转移相比，肺转移中肿瘤浸润性Tfh样细胞高度富集。然而，肺转移中的肿瘤浸润性Tfh样细胞比局部肿瘤中的Tfh样细胞显示出更高的PD-1、TIM-3表达和更低的IL-21表达。总之，本研究确定DTC患者的转移与缺陷Tfh细胞的过度存在有关。
