转移性肾癌中PD-1与Treg的表达及其预后预测价值

摘要

Objectives: To evaluate the tumor-infiltrating PD-1 positive lymphocytes and regulatory T cells (Treg) as prognosis predic-tors of metastatic renal cell carcinoma (mRCC), and investigate the expression of PD-1 and Treg cells in mRCC and elucidate their corre-lation 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 progno-sis. 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 pre-diction for prognosis. Conclusions: Intra-tumoral infiltration of PD-1 positive lymphocytes and Tregs can be used as significant prognos-tic 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.%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(regu-latory 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.