The Prognostic Significance of the Tumor-infiltrating Programmed Cell Death-1 to CD8 Lymphocyte Ratio in Patients with Colorectal Cancer

Background/aim: Tumor-infiltrating lymphocytes (TILs) have been reported to reflect the antitumor immunity of the host and correlate with the therapeutic outcomes and survival. Nowadays TILs are attracting attention as new biomarkers of diseases such as colorectal cancer. TILs are classified into several subsets, among which CD8 T cells directly attack cancer cells and play a central role in antitumor immunity. A high density of CD8 TILs has been reported to correlate with a better clinical outcome. Programmed cell death-1 (PD-1) is recognized to be a surface marker for dysfunction of T lymphocytes. However, the prognostic significance of PD-1 TILs remains unclear. The aim of this study was to evaluate the prognostic significance of the number of PD-1 TILs and the tumor-infiltrating PD-1 to CD8 lymphocyte ratio (PD-1/CD8 ratio) in patients with colorectal cancer (CRC).

Patients And Methods: A total of 90 patients with stage II/III CRC who underwent curative surgery were enrolled in this study. Immunohistochemistry was used to assess the densities of PD-1 TILs and CD8 TILs. The PD-1/CD8 ratio was defined as the number of PD-1 TILs divided by the number of CD8 TILs. The optimum cut-off value for the number of PD-1 TILs and the PD-1/CD8 ratio was determined via a receiver operating characteristic analysis. We then assessed the prognostic significance of the number of PD-1 TILs and the PD-1/CD8 ratio.

Results: The relapse-free and overall survival rates were significantly worse in the high-PD-1/CD8 ratio group than in the low-PD-1/CD8 ratio group (relapse-free survival: p=0.0257, overall survival: p=0.0363), although the number of PD-1 TILs showed no prognostic significance.

Conclusion: The PD-1/CD8 ratio may, therefore, be a useful prognostic marker for stage II/III CRC. What is important for predicting the prognosis may be the PD-1/CD8 ratio rather than the absolute number of PD-1 TILs.