Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Institute for Medical Sciences, Jeonju, Jeonbuk, Republic of Korea.
Transl Oncol. 2013 Jun 1;6(3):282-9. doi: 10.1593/tlo.13256. Print 2013 Jun.
Clear cell renal cell carcinoma (CRCC) is the most common malignant tumor of the kidney, and the clinical outcome of CRCC is related with the metastatic potential of CRCC. A significant proportion of metastatic CRCC remains incurable. Recently, immunotherapy against specific targets such as programmed death 1 (PD1) has been adapted for fatal cases of CRCC.
In this study, we aimed to evaluate the potential of tumor-infiltrating PD1-positive lymphocytes or FoxP3-positive regulatory T cells (Tregs) as predictors of the metastatic potential or prognosis of CRCC and investigate possible correlations with Epstein-Barr virus (EBV) infection in 199 cases of CRCC.
PD1 positivity, high Treg number, and EBV infection all predicted poor overall survival (OS) by univariate analysis. PD1 positivity and high Treg numbers were also significantly correlated with more distant metastatic relapse (DMR) and poor relapse-free survival (RFS) by univariate analysis. PD1 positivity and high Treg number were independent prognostic indicators for OS. In addition, PD1 positivity was an independent predictor of RFS and DMR. EBV infection was an independent predictor of OS of CRCC.
This study demonstrates that intratumoral infiltration of PD1-positive or FoxP3-positive lymphocytes can be used as significant prognostic indicators of CRCC and PD1 positivity could be very helpful in the prediction of latent distant metastasis of CRCCs. Therefore, evaluation of the infiltration of PD-positive cells or Tregs in CRCC may be useful diagnostic tools for the selection of patients who could benefit from PD1- or Treg-based immunotherapy.
透明细胞肾细胞癌（CRCC）是最常见的肾脏恶性肿瘤，CRCC 的临床结局与 CRCC 的转移潜能相关。相当一部分转移性 CRCC 仍然无法治愈。最近，针对程序性死亡 1（PD1）等特定靶点的免疫疗法已被用于治疗致命性 CRCC。
本研究旨在评估肿瘤浸润 PD1 阳性淋巴细胞或 FoxP3 阳性调节性 T 细胞（Tregs）作为 CRCC 转移潜能或预后预测因子的潜力，并探讨其与 199 例 CRCC 中 Epstein-Barr 病毒（EBV）感染的可能相关性。
单因素分析显示，PD1 阳性、Treg 数量高和 EBV 感染均预测总生存期（OS）不良。PD1 阳性和高 Treg 数量也与更远的转移复发（DMR）和较差的无复发生存（RFS）显著相关。PD1 阳性和高 Treg 数量是 OS 的独立预后指标。此外，PD1 阳性是 RFS 和 DMR 的独立预测因子。EBV 感染是 CRCC OS 的独立预测因子。
本研究表明，肿瘤内浸润的 PD1 阳性或 FoxP3 阳性淋巴细胞可作为 CRCC 的重要预后指标，PD1 阳性对预测 CRCC 的潜在远处转移非常有帮助。因此，评估 CRCC 中 PD1 阳性细胞或 Tregs 的浸润可能是选择可能受益于 PD1 或 Treg 为基础的免疫治疗患者的有用诊断工具。
