Abstract
Abstract Backgrounds The tumor microenvironment (TME) is a complex niche for tumor cells and immune cells to survive. Tumor-infiltrating lymphocytes (CD8+ T cells, FoxP3+ Tregs…etc), one of the main components of TME, are key factors in the host-tumor immune response, and the exact immune response in esophageal squamous cell carcinoma (ESCC) is still unclear. The purpose of this study was to investigate the expression of PD-L1 and TILs phenotypes in ESCC, their interactions and clinical significance. Methods Surgical specimens from 126 ESCC patients who underwent curative surgery between January 2001 and April 2017. We performed immunophenotyping of CD4, CD8, CD25, FOXP3 and PD-L1 within the tumor using immunohistochemistry and multiple immunofluorescence immunolabeling. PD-L1 was detected to expressed on tumor cells (PD-L1 TC) and tumor-infiltrating immune cells (PD-L1 TIIC), and PD-L1 TC affect biologic behavior. The calculation of overall survival (OS) and recurrence-free survival (RFS) were made using Kaplan-Meier analysis, and Cox regression model was used to analyze the correlation between survival and prognosis. Results CD8, FoxP3 and PD-L1 expression were positive in 40 (31.7%), 55 (43.7%) and 35 (27.8%) ESCC patient, respectively. CD8 and FoxP3 positive were associated with prolonged OS (p=0.0028, p=0.0324, respectively) and RFS (p=0.0019, p=0.0628, respectively). The overall survival rate in the PD-L1 positive group was statistically lower than that in the negative group (p=0.0402). Furthermore, the combination of CD8/PD-L1 and CD8/Foxp3 was able to more clearly classify and predict prognostic groups of ESCC. Considering the Treg phenotype, the presence of triple positive cell infiltration with Foxp3, CD4, and CD25 was strongly associated with poor prognosis of ESCC (p=0.0349). Cox proportional hazard model suggested that tumor depth, CD8+ infiltration and PD-L1 expression were significantly correlated with overall survival. CD8+ infiltration and PD-L1 expression were revealed to be independent prognostic factors. Conclusion CD8 and PD-L1 expression are independent prognostic and predictive factors for ESCC. And it is necessary to elucidate the immune mechanism comprehensively and thoroughly in the insight of multidimensional, multi-molecular and to provide therapeutic strategies for immunotherapy of ESCC.
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