Programmed Cell Death Ligand 1 Expression Is an Independent Prognostic Factor in Colorectal Cancer (original) (raw)

2018, Anticancer Research

Background/Aim: Programmed cell death protein 1 (PD-1)/ programmed cell death ligand 1(PD-L1) axis is associated with immune tolerance via inhibition of T cell activation. The aim of this study was to clarify the significance of PD-1 and PD-L1 expressions and analyze the relationships between PD-1, PD-L1, transforming growth factor-β (TGF-β) and Forkhead box P3 (Foxp3) expressions in colorectal cancer (CRC). Patients and Methods: A total of 116 patients who underwent curative colectomy for stage II/III CRC were included in the study. PD-1, PD-L1, TGFβ, and Foxp3 expressions were examined by immunohistochemistry and related to prognostic factors by Kaplan-Meier. Results: PD-1 expression was correlated with PD-L1, TGF-β, and Foxp3 expressions. Overall survival rates were significantly poorer in the PD-1 and PD-L1-positive groups. Multivariate analysis showed that PD-L1-positive is an independent risk factor. Disease-free survival (DFS) was tended in the PD-L1-positive group. The group with doublepositive expression had significantly poorer prognosis. Conclusion: PD-1 and PD-L1 expressions were associated with a poor prognosis and correlated with TGF-β and Foxp3 expressions in patients with CRC. Colorectal cancer (CRC) is one of the most common cancers worldwide and the fourth most common cancer in Japan (1, 2). More than 1 million new cases were reported annually resulting in about 600.000 deaths worldwide per year (3). Programmed cell death protein 1 (PD-1) is one of the member of B7/CD28 family, first reported in 1992 (4, 5) and expressed in activated immune cells (4, 6). PD-1 has two ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Each of them has an additional binding partner, B7-1 for PD-L1 and RGMb for PD-L2 (7, 8). PD-1 and its ligand, programmed cell death ligand 1 (PD-L1), interact to suppress T cells activation in many conditions (9). Recently, the significance of PD-1 or PD-L1 expressions were reported in several types of cancers including rectal cancer, skin cancer, gastric cancer, and breast cancer (10-13). Also, we previously reported PD-1 and PD-L1 expression in gastric cancer after curative resection. PD-1 correlated with poor prognosis and associated with transforming growth factor-β (TGFβ) and Forkhead box P3 (FoxP3) expression. However, little is known about the significance of PD-1 and PD-L1 expression in colorectal cancer. The aim of this study was to investigate the role of PD-1 and PD-L1 expression and analyze the relationships among PD-1, PD-L1, Foxp3, and TGF-β expressions in patients with colorectal cancer.