口腔黏膜癌变进程中固有免疫细胞与免疫检查点分子表达趋势验证及交互作用预测
Verification of the expression trend and interaction prediction of innate immune cells and immune-checkpoint molecules in the process of oral mucosal carcinogenesis
作者：李凯玉, 石丽娟, 刘林鑫, 王杰, 聂敏海, 刘旭倩
Author：Li Kaiyu, Shi Lijuan, Liu Linxin, Wang Jie, Nie Minhai, Liu Xuqian
收稿日期：2023-08-29 年卷（期）页码：2024,42(2):192-192-206
期刊名称：华西口腔医学杂志
Journal Name：West China Journal of Stomatology
关键字：口腔黏膜癌变,免疫治疗,免疫逃逸,固有免疫细胞,免疫检查点分子,
Key words：malignant transformation of oral mucosa,immunotherapy,immune escape,inherent immune cells,immune checkpoint molecules,
基金项目：四川省科技计划项目(2022NSFSC0716);泸州市科学技术和人才工作局科技创新领军人才计划(2023RCX171);大学生创新创业训练计划(S202310632340);西南医科大学口腔医学院导师组能力提升计划(2023DS12)
中文摘要
目的 研究口腔黏膜癌变进程中基于数据计算验证的固有免疫细胞和免疫检查点分子的表达趋势，并通过预测其交互作用，探索免疫治疗抑制口腔黏膜癌变进程的方法。 方法 1）利用癌症基因组图谱对口腔黏膜癌变进程中的免疫细胞和免疫检查点分子进行全面评分，筛选出干扰肿瘤细胞免疫逃逸的固有免疫细胞和免疫检查点分子；2）收集血常规资料，对口腔黏膜癌变进程中外周血免疫细胞进行统计学分析，筛选外周血中可能影响口腔黏膜癌变进程的免疫细胞；3）对口腔黏膜癌变进程各阶段中基于数据计算验证的固有免疫细胞和免疫检查点分子进行免疫组织化学染色；4）采用特殊染色鉴定口腔黏膜癌变进程各阶段中基于数据计算验证的固有免疫细胞；5）对口腔黏膜癌变进程中基于数据计算验证的固有免疫细胞和免疫检查点分子进行生存分析，验证固有免疫细胞和免疫检查点分子与口腔鳞状细胞癌预后间的关联。 结果 在口腔黏膜癌变进程中，单核细胞、中性粒细胞表达呈上升趋势；嗜酸性粒细胞表达呈升降单峰趋势；肥大细胞表达呈下降趋势；免疫检查点分子细胞毒性T淋巴细胞相关蛋白4（CTLA4）和细胞程序性死亡-配体1（PD-L1）的表达呈上升趋势。单核细胞、中性粒细胞和嗜酸性粒细胞表达趋势与CTLA4和PD-L1免疫检查点分子的表达趋势正相关；肥大细胞表达趋势与CTLA4和PD-L1免疫检查点分子的表达趋势负相关。单核细胞、中性粒细胞和嗜酸性粒细胞可能促进CTLA4和（或）PD-L1介导的肿瘤细胞免疫逃逸，加速口腔黏膜癌变进程；肥大细胞可能抑制CTLA4和（或）PD-L1介导的肿瘤细胞免疫逃逸，延缓口腔黏膜癌变进程。 结论 干扰固有免疫中特定免疫细胞可在一定程度上调控CTLA4和（或）PD-L1的表达，抑制肿瘤细胞免疫逃逸，延缓口腔黏膜癌变进程。
英文摘要
ObjectiveThis study aimed to explore the expression trends of innate immune cells and immune-checkpoint molecules validated by data calculation in the process of oral mucosal carcinogenesis, as well as to explore methods of suppressing oral mucosal carcinogenesis based on immunotherapy by predicting their interactions.Me-thods 1) The cancer genome atlas (TCGA) database comprehensively scores immune cells and immune-checkpoint molecules in the process of oral mucosal carcinogenesis and screens out intrinsic immune cells and immune-checkpoint molecules that interfere with tumor immune escape. 2) Clinical patient blood routine data were collected for the statistical analysis of peripheral blood immune cells during the progression of oral mucosal carcinogenesis. Immune cells in peripheral blood that may affect the progression of oral mucosal carcinogenesis were screened. 3) Immunohistochemical staining was performed on intrinsic immune cells and immune-checkpoint molecules validated based on data calculation in various stages of oral mucosal carcinogenesis. 4) Special staining was used to identify innate immune cells in various stages of oral mucosal carcinogenesis based on data-calculation verification. 5) Survival analysis was conducted on intrinsic immune cells and immune-checkpoint molecules validated based on data calculation during the process of oral mucosal carcinogenesis. The association of intrinsic immune cells and immune-checkpoint molecules with the prognosis of oral squamous cell carcinoma was verified.ResultsThe expression of monocytes and neutrophils increased during the process of oral mucosal carcinogenesis. The expression of eosinophils showed a single peak trend of up and down. The expression of mast cells decreased. In the process of oral mucosal carcinogenesis, the expression of the immune-checkpoint molecules cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and programmed cell death-ligand (PD-L1) increased. The expression trends of monocytes, neutrophils, and eosinophils were positively correlated with those of CTLA4 and PD-L1 immune-checkpoint molecules. The expression trend of mast cells was negatively correlated with the expression of CTLA4 and PD-L1. Monocytes, neutrophils, and eosinophils may promote tumor immune escape mediated by CTLA4 and/or PD-L1, thereby accelerating the progression of oral mucosal carcinogenesis. Mast cells may inhibit tumor immune escape mediated by CTLA4 and/or PD-L1, delaying the progression of oral mucosal carcinogenesis.ConclusionTherefore, interference with specific immune cells in innate immunity can regulate the expression of CTLA4 and/or PD-L1 to a certain extent, inhibit tumor immune escape, and delay the progression of oral mucosal carcinogenesis.
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