Prognostic value of programmed death-ligand 1 expression in patients with stage III colorectal cancer

Abstract

The programmed death-1/programmed death-ligand 1 (PD-L1) pathway is a negative feedback pathway that suppresses the activity of T cells. Previous studies reported that high PD-L1 expression on tumor cells (TC) was associated with poor survival in patients with colorectal cancer; however, the prognostic evaluation of these studies was limited because they included patients at various disease stages. The purpose of the present study was to evaluate the relationship between PD-L1 status in the immune microenvironment and the clinicopathological features of stage III colorectal cancer. Two hundred and thirty-five patients were included in the analysis. PD-L1 expression on TC and tumor-infiltrating mononuclear cells (TIMC) was evaluated by immunohistochemistry. The median follow-up of thisi study was 52.9 months. A total of 8.1% of stage III colorectal cancer showed high PD-L1 expression on TC and 15.3% showed high PD-L1 expression on TIMC. Patients with high PD-L1 expression on TC had significantly shorter disease-free survival (DFS) than patients with low expression (hazard ratio [HR] 2.36; 95% confidence interval [CI], 1.21-4.62; P = 0.012). In addition, patients with high PD-L1 expression on TIMC were associated with longer DFS than patients with low expression (HR 0.40; 95% CI, 0.16-0.98; P = 0.046). These findings suggest that PD-L1 expression status may be a new predictor of recurrence for stage III colorectal cancer patients and highlight the necessity of evaluating PD-L1 expression on TC and TIMC separately in the tumor microenvironment.

Keywords: CD8-positive T-lymphocytes; colonic neoplasms; immune microenvironment; immunohistochemistry; tumor infiltrating mononuclear cells.

Figure 1

Representative photomicrographs of PD‐L1 expression on tumor cells (TC) and tumor infiltrating mononuclear cells (TIMC) (a), and CD8 positive T cell infiltration in the tumor microenvironment (b). High PD‐L1 expression on TC and low PD‐L1 expression on TIMC (a), low PD‐L1 expression on TC and high PD‐L1 expression on TIMC (b), and low PD‐L1 expression on TC and low PD‐L1 expression on TIMC (c). High CD8 expression in intratumoral and peritumoral cells is present (d), low CD8 expression in intratumoral cells and high CD8 expression in peritumoral cells (e), and low CD8 expression in intratumoral and peritumoral cells (f).

Figure 2

Kaplan–Meier survival analysis of disease‐free survival (DFS) stratified by PD‐L1 expression on tumor cells (TC) (a) and tumor infiltrating mononuclear cells (TIMC) (b).

Figure 3

Kaplan–Meier survival analysis of disease‐free survival (DFS) stratified by intra CD8‐positive T cells/PD‐L1 expression on tumor cells (TC) (a), and peri CD8‐positive T cells/PD‐L1 expression on TC (b).