Tumor-infiltrating PD1-Positive Lymphocytes and FoxP3-Positive Regulatory T Cells Predict Distant Metastatic Relapse and Survival of Clear Cell Renal Cell Carcinoma
Tumor-infiltrating PD1-Positive Lymphocytes and FoxP3-Positive Regulatory T Cells Predict Distant Metastatic Relapse and Survival of Clear Cell Renal Cell Carcinoma
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DOI：
10.1593/tlo.13256
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发表时间：
2013-06-01
影响因子：
5
通讯作者：
Jang, Kyu Yun
中科院分区：
文献类型：
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作者：
Kang, Myoung Jae;Kim, Kyoung Min;Jang, Kyu Yun
背景：透明细胞肾细胞癌（Clear cell renal cell carcinoma， CRCC）是肾脏最常见的恶性肿瘤，其临床预后与CRCC的转移潜能有关。很大比例的转移性CRCC仍然无法治愈。最近，针对特定靶点（如程序性死亡1 (PD1)）的免疫治疗已适用于致命的CRCC病例。材料与方法：在本研究中，我们旨在评估肿瘤浸润性pd1阳性淋巴细胞或foxp3阳性调节性T细胞（Tregs）作为CRCC转移潜力或预后预测因子的潜力，并探讨199例CRCC与eb病毒（EBV）感染的可能相关性。结果：单因素分析显示，PD1阳性、高Treg数和EBV感染均预示总生存期（OS）较差。单因素分析显示，PD1阳性和高Treg数也与更远的转移性复发（DMR）和较差的无复发生存（RFS）显著相关。PD1阳性和高Treg数是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。结论：本研究提示肿瘤内pd - 1阳性或foxp3阳性淋巴细胞浸润可作为CRCC的重要预后指标，pd - 1阳性对预测CRCC的潜在远处转移有很大帮助。因此，评估CRCC中pd阳性细胞或treg的浸润情况可能是选择可能受益于基于PD1或treg的免疫治疗的患者的有用诊断工具。
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.