Zhang Yibo, Xu Liming, Naijibai Momin, Li Jiaoyang, Ling Bin
/ （ 830054） Department of Oral and Maxillofacial Oncology & Surgery, The First Affiliated Hospital/Hospital of Stomatology, Xinjiang Medical University, Urumqi 830054, China.
（ 830054） Stomatological Research Institute of Xinjiang Autonomous Region, Urumqi 830054, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2025 May 20;56(3):746-753. doi: 10.12182/20250560602.
To investigate the role of () in the tumor microenvironment of oral squamous cell carcinoma (OSCC) and provide new insights for OSCC treatment.
The murine squamous cell carcinoma cell line SCC7 was cultured , and a tumor-bearing model was established with C57BL/6 mice. Experimental mice were randomly assigned to the activation group and the control group ( = 5 per group) based on the principles of randomization and control. After 16 days of feeding, the mice were sacrificed, and the weight and volume of the tumors in the two groups of mice were recorded. Immunohistochemistry was performed to analyze the expression levels of CD4 T cells, CD8 T cells, transforming growth factor-β (TGF-β), interleukin-10 (IL-10), interferon-γ (IFN-γ), E-cadherin, N-cadherin, Twist, vascular endothelial growth factor (VEGF), CD31, and Ki67 in the tumor tissues. Flow cytometry was performed to examine the tumor samples from the two groups of mice, and to quantify the proportional differences of CD4 T cells, CD8 T cells, as well as CD69 and CD103 on T lymphocytes from the samples.
The immunohistochemistry results showed that the expression of CD4 T cells and their function-related cytokines in the tumor tissues of the activation group was higher than that of the control group, and the differences were statistically significant ( < 0.05). According to the flow cytometry results, the proportion of CD8 T cells in the tumor tissues of the activation group decreased, and the proportion of CD103CD8 T cells, which played an anti-tumor immune role, also decreased, with the differences being statistically significant compared with the control group ( < 0.05). In addition, the expression of all the cytokines associated with malignant tumor phenotypes in the activation group increased, and the differences were statistically significant compared with the control group ( < 0.05).
This study verified through animal experiments that by enhancing the infiltration of CD4 T cells and suppressing the immunosuppressive function of CD8 T cells in the OSCC tumor microenvironment, enables tumor cell immune escape and accelerates epithelial-mesenchymal transition, angiogenesis, and tumor cell proliferation.
探讨（）在口腔鳞状细胞癌（OSCC）肿瘤微环境中的作用，为OSCC治疗提供新的见解。
培养小鼠鳞状细胞癌细胞系SCC7，并建立C57BL/6小鼠荷瘤模型。根据随机化和对照原则，将实验小鼠随机分为激活组和对照组（每组n = 5）。饲养16天后，处死小鼠，记录两组小鼠肿瘤的重量和体积。采用免疫组织化学法分析肿瘤组织中CD4 T细胞、CD8 T细胞、转化生长因子-β（TGF-β）、白细胞介素-10（IL-10）、干扰素-γ（IFN-γ）、E-钙黏蛋白、N-钙黏蛋白、Twist、血管内皮生长因子（VEGF）、CD31和Ki67的表达水平。采用流式细胞术检测两组小鼠的肿瘤样本，定量分析样本中T淋巴细胞上CD4 T细胞、CD8 T细胞以及CD69和CD103的比例差异。
免疫组织化学结果显示，激活组肿瘤组织中CD4 T细胞及其功能相关细胞因子的表达高于对照组，差异具有统计学意义（P < 0.05）。流式细胞术结果显示，激活组肿瘤组织中CD8 T细胞比例降低，发挥抗肿瘤免疫作用的CD103⁺CD8 T细胞比例也降低，与对照组相比差异具有统计学意义（P < 0.05）。此外，激活组中所有与恶性肿瘤表型相关的细胞因子表达均增加，与对照组相比差异具有统计学意义（P < 0.05）。
本研究通过动物实验证实，（）通过增强OSCC肿瘤微环境中CD4 T细胞的浸润并抑制CD8 T细胞的免疫抑制功能，使肿瘤细胞发生免疫逃逸，加速上皮-间质转化、血管生成和肿瘤细胞增殖。
