关键词: 口腔鳞状细胞癌, T淋巴细胞, 糖酵解, 活性氧, 低氧诱导因子-1

Abstract: Objective:To explore the effect of reactive oxygen species (ROS) on the differentiation of tumor infiltrating T lymphocytes in oral squamous cell carcinoma (OSCC). Methods: The proportion of T lymphocyte subsets in tumor and distal normal tissue were analyzed by flow cytometry. ROS expression was analyzed with ROS kit. Genes associated with T cell metabolism (HIF1A, GLUT1, HK2) in carcinoma and distal normal tissues were quantified by real time qPCR. GEPIA2 database was used to analyze the differential expression of T cell HIF1A in tumor and distal normal tissues and the prognosis value of mRNA level of T cell HIF1A in patients. Results: The proportion of effectors T cells (CD45RA+ CCR7?) in cancer tissues was significantly higher than that in distal normal tissues (P<0.05). The abundance of ROS in CD3+ T cells in cancer tissues was higher than that in distal normal tissues (P<0.05), and in cancer tissues, the ROS was significantly accumulated in effector T cells up-regulated compared with its counterpart in effector memory T cells (P<0.05). There were no statistically significant differences of ROS between the effector T cell and effector memory T cell in the distal normal tissue (P>0.05). Expressions of HIF1A, GLUT1, HK2 in tumor-infiltrating T cells were higher in those in distal normal tissues (P<0.05). T cell HIF1A level was higher in tumor tissues than that in distal normal tissues, but no significant statistical difference was found. The HIF1A level of effector T cells in tumor tissues was significantly higher than that in distal normal tissues (P<0.05). Patients with higher expression of HIF1A in T cell have a better prognosis (P<0.05). Conclusions:The upregulation of ROS/HIF-1 signaling pathway in the OSCC tumor microenvironment was significantly correlated with the high proportion of effector T lymphocytes in tumor tissues.

Key words: oral squamous cell carcinoma, T lymphocyte, glycolysis, reactive oxygen species, HIF - 1