Clinical impact of Fn-induced high expression of KIR2DL1 in CD8 T lymphocytes in oesophageal squamous cell carcinoma

Abstract

Background To analyze the correlation between the inducing effect of Fusobacterium nucleatum (Fn) on the surface expression of the inhibitory receptor KIR2DL1 on CD8+ T cells in oesophageal squamous cell carcinoma (ESCC) and the clinicopathological features and survival prognosis and to explore its clinical significance. Methods The inducing effect of Fn on CD8+ T cell surface inhibitory receptor KIR2DL1 expression was analyzed in a coculture system of human CD8+ T cells and ESCC cells infected with Fn. Fn infection and the expression of KIR2DL1 on CD8+ T cells were detected by RNAscope and immunohistochemistry in ESCC tissues, and the correlations between the inducing effect of Fn on KIR2DL1 expression on CD8+ T cells and clinicopathological features were analyzed. COX regression was used to analyze the influence of each factor on the prognosis of ESCC. Survival curves were plotted by the Kaplan–Meier method, and the effect of KIR2DL1 induction on survival time was analyzed by the log-rank test. Results In the coculture system, KIR2DL1 expression on the surface of CD8+ T cells increased with increasing Fn infection time. In ESCC tissues, Fn infection was significantly correlated with high KIR2DL1 expression on CD8+ T cells. The Fn + CD8+KIR2DL1 positive patients were predominantly males who were smokers and alcohol drinkers. Moreover, patients with Fn infection were characterized by poor tumour differentiation, advanced clinical stage, and a short survival time. Meanwhile, Fn + CD8+KIR2DL1 positive group was independent risk factor affecting the prognosis of ESCC patients. Conclusions Long-term drinking and smoking lead to an extremely unhealthy oral environment in which Fn infection and colonization are more likely to occur, thus inducing high expression of KIR2DL1 on the surface of CD8+ T cells, which can weaken the antitumour immune response and promote the malignant progression of ESCC.HIGHLIGHTS Fn induced high expression of KIR2DL1 CD8+ T cells in a time-dependent manner. Fn can reduce the response of tumour cells to CDDP. The inducing effect of Fn on CD8+ T cell surface KIR2DL1 expression was significantly associated with the poor prognosis of ESCC patients.

Keywords

• fusobacterium nucleatum
• oesophageal squamous cell carcinomas
• cd8+ t lymphocytes
• kir2dl1
• prognosis