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FoxP3促进合并桥本甲状腺炎的甲状腺乳头状癌患者的淋巴结转移。

FoxP3 promotes lymph node metastasis in patients with papillary thyroid carcinoma complicated with Hashimoto's thyroiditis.

作者信息

Zeng Rong, Lyu Yi, Niu Heng, Yang Kunxian, Yan Xinmin

机构信息

Department of Medical Oncology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China.

Department of Anesthesiology, Minhang Hospital, Fudan University, Shanghai 200032, China.

出版信息

Transl Cancer Res. 2020 Mar;9(3):1337-1350. doi: 10.21037/tcr.2020.01.12.

Abstract

BACKGROUND

To investigate the effect of Treg cells on patients with PTC complicated with HT.

METHODS

We collected thyroid fresh tissue of human after surgery, paraffin tissue and serum samples (cancer tissue which was diagnosed by pathology). Analysed the expression of nuclear specific marker gene FoxP3 in Treg cells by Envision immunohistochemical staining. Transwell cell chamber was used to simulate the co-action environment of umbilical cord blood initial T lymphocytes and thyroid papillary carcinoma cells (TPC-1and K1). Compared with human normal thyroid follicular epithelial cell line Nthy-ori 3-1. Flow cytometry was used to detect the proportion of Treg cells (CD4CD25CD127/CD4CD25%) at 0, 24, 36, 48, 60 h after co-administration of thyroid papillary carcinoma cell lines (TPC-1 and K1) and umbilical cord blood initial T lymphocytes. The expression of FoxP3 protein in co-acting T lymphocytes was detected by Western blot.

RESULTS

The results showed that the positive expression of FoxP3 in the tumor microenvironment of PTC patients with or without HT promoted lymph node metastasis of tumors and played a role in inhibiting tumor immunity. PTC cancer cells could induce initial T lymphocyte differentiating into Treg cells. At 36 h, the ratio of Th17 cells and Treg cells which were differentiated was the highest. The balance of Th17/Treg was significantly biased toward Th17. The proportion of FoxP3 induced by K1 cell line with lymph node metastasis was higher than that of TPC-1 cell line without lymph node metastasis.

CONCLUSIONS

FoxP3 could promote lymph node metastasis to inhibit tumor immunity by dysregulation of Th17/Treg balance in PTC patients complicated with HT.

摘要

背景

探讨调节性T细胞(Treg细胞)对合并桥本甲状腺炎(HT)的甲状腺乳头状癌(PTC)患者的影响。

方法

收集人类术后甲状腺新鲜组织、石蜡组织及血清样本(经病理诊断的癌组织)。采用Envision免疫组化染色分析Treg细胞中核特异性标志物基因FoxP3的表达。利用Transwell细胞小室模拟脐血初始T淋巴细胞与甲状腺乳头状癌细胞(TPC-1和K1)的共同作用环境,与人类正常甲状腺滤泡上皮细胞系Nthy-ori 3-1进行比较。采用流式细胞术检测甲状腺乳头状癌细胞系(TPC-1和K1)与脐血初始T淋巴细胞共同作用0、24、36、48、60小时后Treg细胞(CD4CD25CD127/CD4CD25%)的比例。通过蛋白质免疫印迹法检测共同作用的T淋巴细胞中FoxP3蛋白的表达。

结果

结果显示,合并或未合并HT的PTC患者肿瘤微环境中FoxP3的阳性表达促进肿瘤淋巴结转移并发挥抑制肿瘤免疫的作用。PTC癌细胞可诱导初始T淋巴细胞分化为Treg细胞。在36小时时,分化的Th17细胞与Treg细胞的比例最高。Th17/Treg平衡显著偏向Th17。有淋巴结转移的K1细胞系诱导的FoxP3比例高于无淋巴结转移的TPC-1细胞系。

结论

在合并HT的PTC患者中,FoxP3可通过失调Th17/Treg平衡促进淋巴结转移以抑制肿瘤免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04c6/8797984/e02d57cff70c/tcr-09-03-1337-f1.jpg

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