Classification of gallbladder cancer by assessment of CD8+ TIL and PD-L1 expression

Background: Programmed death ligand 1/2 (PD-L1/PD-L2) expression has been established as a prognostic factor for various solid tumors and as a predictive factor for PD-1 blockade therapy, but scant data on its role in gallbladder cancer (GBC). The aims of this study were to assess the expression of PD-L1/PD-L2 and the density of CD8(+) tumor-infiltrating lymphocytes (TIL) from GBC samples and to quantify the association between survival prognosis and these factors. Methods: CD8(+) TILs density and the expression of PD-1, PD-L1, PD-L2 and CD133 were assessed using immunohistochemistry in tumor specimens from 66 patients with gallbladder adenocarcinoma. These indexes were correlated with the clinicopathological features. Results: The rate of PD-L1-positive (PD-L1(+)) was 54%, which included 18% positivity in tumor cells, and 36% in peritumoral immune stroma. High CD8(+) TIL density (CD8(high)) was observed in PD-L1(+) GBC, and PD-L+ was positively associated with PD-L2(+) expression. Regarding prognostic factors, PD-L1(+) expression was related to worse overall survival (OS), and CD8(high) indicated better OS and progression-free survival (PFS). The combination of CD8(high )with PD-L1(+) serves as a prognostic factor for improved OS (P < 0.001) and PFS (P = 0.014). Conclusion: Analysis of the tumor immune microenvironment based on CD8(+) TIL and PD-L1 expression is a promising independent predictor for the clinical outcome of GBC patients.