肿瘤浸润程序性细胞死亡蛋白1与CD8淋巴细胞比值在结直肠癌患者中的预后意义
The Prognostic Significance of the Tumor-infiltrating Programmed Cell Death-1 to CD8 Lymphocyte Ratio in Patients with Colorectal Cancer.
作者信息
Shibutani Masatsune, Maeda Kiyoshi, Nagahara Hisashi, Fukuoka Tatsunari, Nakao Shigetomi, Matsutani Shinji, Hirakawa Kosei, Ohira Masaichi
机构信息
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
出版信息
Anticancer Res. 2017 Aug;37(8):4165-4172. doi: 10.21873/anticanres.11804.
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.
背景/目的：据报道，肿瘤浸润淋巴细胞（TILs）可反映宿主的抗肿瘤免疫力，并与治疗效果和生存率相关。如今，TILs作为结直肠癌等疾病的新生物标志物正受到关注。TILs可分为几个亚群，其中CD8 T细胞直接攻击癌细胞，在抗肿瘤免疫中起核心作用。据报道，高密度的CD8 TILs与更好的临床结果相关。程序性细胞死亡蛋白1（PD-1）被认为是T淋巴细胞功能障碍的表面标志物。然而，PD-1 TILs的预后意义仍不清楚。本研究的目的是评估结直肠癌（CRC）患者中PD-1 TILs数量和肿瘤浸润性PD-1与CD8淋巴细胞比率（PD-1/CD8比率）的预后意义。
患者与方法
本研究共纳入90例接受根治性手术的II/III期CRC患者。采用免疫组织化学法评估PD-1 TILs和CD8 TILs的密度。PD-1/CD8比率定义为PD-1 TILs数量除以CD8 TILs数量。通过受试者工作特征分析确定PD-1 TILs数量和PD-1/CD8比率的最佳截断值。然后，我们评估了PD-1 TILs数量和PD-1/CD8比率的预后意义。
结果
高PD-1/CD8比率组的无复发生存率和总生存率显著低于低PD-1/CD8比率组（无复发生存率：p=0.0257，总生存率：p=0.0363），尽管PD-1 TILs数量无预后意义。
结论
因此，PD-1/CD8比率可能是II/III期CRC的一个有用的预后标志物。预测预后的重要因素可能是PD-1/CD8比率，而不是PD-1 TILs的绝对数量。
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