转移性肾癌中PD-1与Treg的表达及其预后预测价值

  目的  旨在评估肿瘤浸润性程序性死亡受体-1（programmed cell death protein-1，PD-1）阳性淋巴细胞及调节性T细胞（regulatory T cell，Treg）对转移性肾癌（metastatic renal cell carcinoma，mRCC）预后的预测价值。探讨PD-1和Treg在mRCC中的表达及其与患者临床病理参数、预后的相关性。  方法  收集2007年6月至2017年6月269例复旦大学附属中山医院mRCC患者的临床病理资料，应用免疫组织化学法检测mRCC患者组织中PD-1和Treg的表达，分析其与各项临床指标及预后的关系。  结果  mRCC患者组织中PD-1表达的阳性率为31.60%（85/269），表达水平与肿瘤Fuhrman分级呈正相关，与预后呈负相关；Treg表达的阳性率为36.80%（99/269），表达水平亦与肿瘤Fuhrman分级呈正相关，与预后呈负相关。单因素分析显示，PD-1阳性和高Treg浸润数量与总生存（overall survival，OS）率及无进展生存（progression free survival，PFS）率呈负相关。PD-1阳性和高Treg浸润数量为OS和PFS的独立预后指标，二者联合可起到较好的预测效果。  结论  PD-1阳性或高Treg浸润数量可作为mRCC的预后指标，二者联合预测效果更佳。mRCC患者组织中PD-1阳性淋巴细胞或Treg浸润数量的评估可为临床预后判断提供依据。 

Expression and prognostic value of PD-1 and Tregs in metastatic renal cell carcinoma

  Objectives  To evaluate the tumor-infiltrating PD-1 positive lymphocytes and regulatory T cells (Treg) as prognosis predictors of metastatic renal cell carcinoma (mRCC), and investigate the expression of PD-1 and Treg cells in mRCC and elucidate their correlation with clinicopathological parameters and prognosis.  Methods  A total of 269 mRCC patients from June 2007 to June 2017 in Zhongshan Hospital, Fudan University, were included in the study. The expression of PD-1 and Tregs in mRCC samples were detected by immunohistochemistry. The relationship between the expression of PD-1 and Tregs was analyzed.  Results  PD-1 positive expression in mRCC was 31.60% (85/269) and it was positively correlated with the tumor Fuhrman grade and negatively correlated with prognosis. Tumor infiltration of Tregs in mRCC was 36.80% (99/269), and it was also positively correlated with the tumor Fuhrman grade and negatively correlated with prognosis. Univariate analysis showed that PD-1 positive lymphocytes and high Treg infiltration numbers were negatively correlated with overall survival (OS) and progression free survival (PFS) rates. Thus, PD-1 positive lymphocytes and high Treg infiltration numbers are independent prognostic indicators of OS and PFS and when combined, they can render a better prediction for prognosis.  Conclusions  Intra-tumoral infiltration of PD-1 positive lymphocytes and Tregs can be used as significant prognostic indicators of mRCC, and the combined predictive effect is better than the individual predictive effect. Therefore, evaluating the number of PD-1 positive lymphocytes or infiltrating Tregs in mRCC is helpful in clinically estimating mRCC prognosis in patients.