The Expression Of PD-1/PD-L1 In Esophageal Cancer Tissue And Its Influence On Prognosis Of Esophageal Cancer

Objective:In China, esophageal cancer is one of the most common malignant tumors, of which more than 90% are esophageal squamous cell carcinoma. Currently surgery is still the standard treatment for resectable esophageal squamous cell carcinoma. Local recurrence or distant metastasis is the main cause of treatment failure. Now we use clinicopathological parameters, such as histological type, tumor size, tumor staging, to evaluate the prognosis of esophageal squamous cell carcinoma patients. Therefore, search for new biomarkers to predict the prognosis and guide clinical management of esophageal cancer is very important. PD-1 is an inhibitory costimulatory molecules belonging to B7: CD28 family. It is expressed primarily in activated T cells, B cells, natural killer cells(NK), activated monocytes, natural killer T cells(NKT), part of the dendritic cells(DCs). PD-1 has two ligands PD-L1 and PD-L2, PD-L1 is expressed on T cells, B cells, macrophages, mesenchymal stem cells, DCs cells, and bone marrow-derived mast cells. PD-L1 is the major PD-1 ligand expressed in solid tumors. PD-1/PD-L pathway plays an important role in tumor immunity. Our study used immunohistochemical method to explore the relationship between PD-1/PD-L1 expression and prognosis in patients with esophageal cancer.Methods:1.Immunohistochemistry was used to detect the expression of PD-1/PD-L1 in esophageal carcinoma. Correlation between PD-1/PD-L1 expression and clinicopathological parameters is analyzed.2.Immunohistochemistry was used to detect tumor infiltrating lymphocytes(CD8+T, Foxp3+T) expression in esophageal cancer. Correlation between tumor PD-1/PD-L1 expression and TILs was analyzed.3.Relationship between PD-1/PD-L1 expression and prognosis in patients with esophageal cancer was analyzed by Log-rank test.4.Cox regression was performed for multivariate analysis.Results:1.Expression of PD-1 / PD-L1 in esophageal carcinomaOf the 50 tumors evaluated in this study, 27(54%) were positive for PD-L1 expression at protein level and 23(46%) were negative, whereas PD-1 was positive in 24(52%) and negative in 26(48%). PD-L1 were expressed mainly on cancer cells and it was also found in some infiltrating lymphocytes as well as stromal cells. In addition, PD-1was expressed mainly on infiltrating lymphocytes(Fig. 1).2.Correlation between PD-1/PD-L1 expression and clinicopathological parameters?~2 test was used to analyze correlation between PD-1/PD-L1 expression and clinicopathological parameters. No significant association was observed between PD-1/PD-L1 expression and the clinicopathological variables(Table 1).3.Correlation between tumor PD-1/PD-L1 expression and TILsThe Correlation between PD-1/PD-L1 and TILs was analyzed by Spearman's test. The results showed that both PD-1 and PD-L1 expression was positively correlated with CD8 + T lymphocytes(P = 0.006, P = 0.003). There was no significant correlation between PD-1/PD-L1 expression and Foxp3 + T cells(P = 0.749, P = 0.186)(Table 2).4.Prognostic value of PD-1/PD-L1 expressionProgression-free survival(PFS) rates were similar in PD-1 positive group and PD-1 negative group.(p=0.459)(Fig. 3). However, PFS was significantly poorer in the PD-L1 positive group than in the PD-L1 negative group(p=0.048)(Fig. 2). Cox regression was performed for multivariate analysis. As a result, T stage and PD-L1 expression is an independent predictor of PFS(P = 0.007, P = 0.035).Conclusion:1.PD-L1 expression can be used as an independent predictor of PFS in esophageal squamous cell carcinoma.2.PD-1/PD-L1 expression was positively correlated with CD8+T lymphocytes in esophageal squamous cell carcinoma.