Xu Liming, Tian Xiao, Wang Jie, Zhang Yibo, Naijibai Momin, Ling Bin
/ ， （ 830054） Department of Oral and Maxillofacial Oncology & Surgery, The First Affiliated Hospital/Hospital of Stomatology, Xinjiang Medical University and Stomatological Research Institute of Xinjiang Autonomous Region, Urumqi 830054, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2025 Jan 20;56(1):191-197. doi: 10.12182/20250160105.
To investigate the mechanisms by which () promotes the malignant progression of oral squamous cell carcinoma (OSCC) through the recruitment of chemokine receptor 6-positive (CCR6) regulatory T cells (Treg) in the tumor microenvironment (TME).
The Cancer Genome Atlas (TCGA) database was used to analyze the correlation between chemokine ligand 20 (CCL20), CCR6, and Treg. The Treg enrichment index and the expression levels of interleukin (IL)-10 and tumor necrosis factor β1 (TGF-β1) were assessed in the high CCR6 expression group of OSCC patients. C57BL/6 mice were randomly assigned to a control group and an experimental group ( = 6 in each group). The control group received a single injection of 100 μL SCC7, a mice head and neck squamous carcinoma cell line, while the experimental group received a single injection of 100 μL mixture of SCC7 cells and in the cheek. After two weeks, the mice were sacrificed, and immunohistochemistry was performed to assess the expression levels of CCR6 and forkhead box protein 3 (FOXP3) in OSCC. Flow cytometry was performed to analyze the effects of on OSCC malignant biological behavior, CCR6 Treg cells, and the immune microenvironment.
Bioinformatics analysis revealed a correlation between CCL20, CCR6, and Treg ( = 0.373, < 0.000 1). OSCC patients with high CCR6 expression showed higher Treg enrichment scores and increased IL-10 expression. Animal experiments showed that promoted the increase in the tumor volume (mm) (0.294 ± 0.105 in the control group and 0.526 ± 0.101 in the experimental group, < 0.01) and mass (mg) (206.200 ± 53.950 in the control group and 376.000 ± 119.200 in the experimental group, < 0.01) in mice with OSCC. Immunohistochemistry confirmed a correlation between CCR6 and FOXP3 ( = 0.659, < 0.05), and promoted the expression of CCR6 and FOXP3. Flow cytometry analysis showed that increased the proportion of CCR6 Treg (%) (13.780 ± 1.506 in the control group and 18.260 ± 2.257 in the experimental group, < 0.01) and decreased the proportion of CD8 T cells (%) (27.120 ± 1.647 in the control group and 21.060 ± 3.148 in the experimental group, < 0.01) in OSCC, thereby promoting the formation of a immunosuppressive microenvironment.
promotes the malignant progression of OSCC by recruiting CCR6 Treg cells to form an immunosuppressive TME.
探讨（）通过募集肿瘤微环境（TME）中趋化因子受体6阳性（CCR6）调节性T细胞（Treg）促进口腔鳞状细胞癌（OSCC）恶性进展的机制。
利用癌症基因组图谱（TCGA）数据库分析趋化因子配体20（CCL20）、CCR6和Treg之间的相关性。评估OSCC患者CCR6高表达组中的Treg富集指数以及白细胞介素（IL）-10和肿瘤坏死因子β1（TGF-β1）的表达水平。将C57BL/6小鼠随机分为对照组和实验组（每组n = 6）。对照组单次注射100 μL SCC7（一种小鼠头颈鳞状癌细胞系），而实验组在脸颊单次注射100 μL SCC7细胞与（）的混合物。两周后，处死小鼠，进行免疫组织化学以评估OSCC中CCR6和叉头框蛋白3（FOXP3）的表达水平。进行流式细胞术分析（）对OSCC恶性生物学行为、CCR6 Treg细胞和免疫微环境的影响。
生物信息学分析显示CCL20、CCR6和Treg之间存在相关性（r = 0.373，P < 0.000 1）。CCR6高表达的OSCC患者表现出更高的Treg富集分数和IL-10表达增加。动物实验表明，（）促进了OSCC小鼠肿瘤体积（mm）的增加（对照组为0.294 ± 0.105，实验组为0.526 ± 0.101，P < 0.01）和肿瘤质量（mg）的增加（对照组为206.200 ± 53.950，实验组为376.000 ± 119.200，P < 0.01）。免疫组织化学证实CCR6与FOXP3之间存在相关性（r = 0.659，P < 0.05），并且（）促进了CCR6和FOXP3的表达。流式细胞术分析表明，（）增加了OSCC中CCR6 Treg的比例（%）（对照组为13.780 ± 1.506，实验组为18.260 ± 2.257，P < 0.01），并降低了CD8 T细胞的比例（%）（对照组为27.120 ± 1.647，实验组为21.060 ± 3.148，P < 0.01），从而促进了免疫抑制微环境的形成。
（）通过募集CCR6 Treg细胞形成免疫抑制性TME促进OSCC的恶性进展。
