調節性T細胞與介白素-1β、介白素-6以及變形生長因子-β於口腔鱗狀上皮細胞癌之表現

Abstract

Background: The occurrence and progression of oral squamous cell carcinoma (OSCC) are highly correlated with inflammation, which is mediated by pro-inflammatory cytokines, including interleukin-1β (IL-1β) and interleukin-6 (IL-6). But the adaptive immune cells are suppressed in the tumor microenvironment. Regulatory T cells (Tregs) suppress immune response through transforming growth factor-β (TGF-β) mediation. Tregs may suppress inflammatory response and help the control of tumor, but also may support tumor to escape from immune surveillance and promote tumor progression. The study was to investigate the expression of Treg and TGF-β, which exert anti-inflammation, and IL-1β and IL-6, which promote inflammatory response in OSCC and their associations with clinical and pathological features. Materials and methods: Surgical specimens from 71 patients treated for OSCC at Department of Oral and Maxillofacial Surgery, National Taiwan university hospital, were evaluated for Foxp3, TGF-β, IL-1β and IL-6 expression by immunihistochemical staining. The expression of Foxp3, TGF-β, IL-1β and IL-6 in OSCC cancer and stromal cells were evaluated respectively. Associations of Foxp3, TGF-β, IL-1β and IL-6 expression with clinical and pathological features were evaluated by using Pearson product-moment correlation coefficient, Student’s t test, Kruskal-Wallis H test and Mann-Whitney U test. Associations of Foxp3, TGF-β, IL-1β and IL-6 expression with survival of patients from OSCC were evaluated by using Kaplan-Meier survival analysis. Results: All patients showed Foxp3 and IL-6 expression. IL-1β and TGF-β have one case didn’t show any positive expression in tumor and stromal cells respectively. The expression of Foxp3, TGF-β, IL-1β and IL-6 were correlated with themselves or each others. Compared early stage with advanced stage tumor, the expression of Foxp3 was higher in early stage, and the expression of IL-1β in tumor cells was higher in advanced stage. The higher expression of TGF-β in tumor cells was associated with better cumulative proportion surviving. Conclusions：OSCC is a highly associated with inflammatory response, and the expression of IL-1β was higher in more invasively tumor, and Foxp3 expression was higher in early stage tumor. If the patients had smoking and/or alcohol drinking and/or betel quid chewing, the expression of IL-1β was higher in cancer cells and IL-6 was higher in stromal cells, but the amount of Tregs were lower. This result indicates that these habits deviate tumor to more inflammatory microenvironment. If over 50% tumor cells express TGF-β, the cumulative proportion surviving would be higher, indicating TGF-β associated with better prognosis. In this study, the expression of Foxp3, IL-1β, IL-6 have no impact on the survival and prognosis of OSCC.