PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma
PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma
复制标题
程序性死亡受体1（PD - 1）由肿瘤浸润免疫细胞表达，且与肾细胞癌患者的不良预后相关。
DOI：
10.1158/1078-0432.ccr-06-2599
复制
发表时间：
2007-03-15
影响因子：
11.5
通讯作者：
Kwon, Eugene D.
中科院分区：
文献类型：
--
作者：
Thompson, R. Houston;Dong, Haidong;Kwon, Eugene D.
目的：B7-H1 在临床侵袭性肾细胞癌 (RCC) 中表达，可预测不良后果。已知 B7-H1 通过与程序性死亡 1 (PD-1) 受体相互作用损害宿主免疫力，该受体由激活的 T 细胞表达。尚未评估临床 RCC 肿瘤中表达 PD-1 (PD-1(+)) 的免疫细胞的水平。因此，我们测试了在侵袭性 RCC 肿瘤中是否观察到免疫细胞 PD-1 表达。 实验设计：2000 年至 2003 年间，267 名患者在我们的机构因透明细胞 RCC 接受了肾切除术，并有新鲜冷冻组织可供检查。使用抗 PD-1（克隆 MIH4）对这些 RCC 标本进行免疫染色，并进行结果分析。结果：在 136 份（50.9%）标本中观察到单核免疫细胞浸润。 PD-1+ 免疫细胞存在于这 136 个肿瘤中的 77 个（56.6%）中。相反，RCC肿瘤细胞不表达PD-1。具有PD-1（+）免疫细胞的患者明显更有可能携带B7-H1（+）肿瘤细胞（P < 0.001）、更大的肿瘤（P = 0.001）和更高核级别的肿瘤（P = 0.001）。同样，肿瘤内PD-1（+）免疫细胞与晚期肿瘤淋巴结转移阶段（P = 0.005）、凝固性肿瘤坏死（P = 0.027）和肉瘤样分化（P = 0.008）相关。中位随访时间为 2.9 年，52 名患者死于 RCC。单变量显示，与 PD-1(-) 患者相比，PD-1(+) 免疫细胞患者存在显着的癌症特异性死亡风险（风险比为 2.24；P = 0.004）。结论：高危 RCC 肿瘤患者中表达 PD-1 的免疫细胞水平升高。免疫细胞 PD-1 和 B7-H1 之间的相互作用可能会导致肾细胞癌患者的免疫功能障碍，从而促进癌症进展。
Purpose: B7-H1 is expressed by clinically aggressive forms of renal cell carcinoma (RCC) and predicts adverse outcome. B7-H1 is known to impair host immunity via interaction with the Programmed Death-1 (PD-1) receptor, which is expressed by activated T cells. Levels of immune cells expressing PD-1 (PD-1(+)) in clinical RCC tumors have not been evaluated. Thus, we tested whether immune cell PD-1 expression is observed within aggressive RCC tumors.Experimental Design: Between 2000 and 2003, 267 patients underwent nephrectomy at our institution for clear cell RCC and had fresh-frozen tissue available for review. These RCC specimens were immunostained using anti-PD-1 (clone MIH4) and outcome analyses were conducted.Results: Mononuclear immune cell infiltration was observed in 136 (50.9%) specimens. PD-1+ immune cells were present in 77 of these 136 (56.6%) tumors. In contrast, RCC tumor cells did not express PD-1. Patients with PD-1(+) immune cells were significantly more likely to harbor B7-H1(+) tumor cells (P < 0.001), larger tumors (P = 0.001), and tumors of higher nuclear grade (P = 0.001). Likewise, intratumoral PD-1(+) immune cells were associated with advanced tumor-node-metastasis stage (P = 0.005), coagulative tumor necrosis (P = 0.027), and sarcomatoid differentiation (P = 0.008). With a median follow-up of 2.9 years, 52 patients died from RCC. Univariately, patients with PD-1(+) immune cells were at significant risk of cancer-specific death compared with PD-1(-) patients (risk ratio, 2.24; P = 0.004).Conclusions: Levels of immune cells expressing PD-1 were increased in patients with high-risk RCC tumors. Interactions between immune cell PD-1 and B7-H1 may promote cancer progression by contributing to immune dysfunction in patients with RCC.