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

Masatsune Shibutani; Kiyoshi Maeda; Hisashi Nagahara; Tatsunari Fukuoka; Shigetomi Nakao; Shinji Matsutani; Kosei Hirakawa; Masaichi Ohira

doi:10.21873/anticanres.11804

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

Anticancer Res. 2017 Aug;37(8):4165-4172. doi: 10.21873/anticanres.11804.

Authors

Masatsune Shibutani¹, Kiyoshi Maeda², Hisashi Nagahara², Tatsunari Fukuoka², Shigetomi Nakao², Shinji Matsutani², Kosei Hirakawa², Masaichi Ohira²

Affiliations

¹ Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan fbxbj429@ybb.ne.jp.
² Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.

PMID: 28739701
DOI: 10.21873/anticanres.11804

Abstract

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.

Keywords: CD8; Colorectal cancer; prognosis; programmed cell death-1; tumor-infiltrating lymphocyte.

MeSH terms

Adult
Aged
Aged, 80 and over
CD8 Antigens / genetics*
CD8-Positive T-Lymphocytes / metabolism
CD8-Positive T-Lymphocytes / pathology
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / pathology
Female
Humans
Kaplan-Meier Estimate
Lymphocytes, Tumor-Infiltrating / metabolism
Lymphocytes, Tumor-Infiltrating / pathology*
Male
Middle Aged
Neoplasm Recurrence, Local / genetics
Neoplasm Recurrence, Local / pathology
Neoplasm Staging
Prognosis
Programmed Cell Death 1 Receptor / genetics*
T-Lymphocyte Subsets / metabolism
T-Lymphocyte Subsets / pathology

Substances

CD8 Antigens
PDCD1 protein, human
Programmed Cell Death 1 Receptor