Peters I, Tezval H, Kramer M W, Wolters M, Grünwald V, Kuczyk M A, Serth J
Klinik für Urologie und Urologische Onkologie, Medizinische Hochschule Hannover, Hannover.
Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover.
Aktuelle Urol. 2015 Nov;46(6):481-5. doi: 10.1055/s-0041-106169. Epub 2015 Nov 11.
The era of cytokines, given to patients with metastatic renal cell carcinoma (mRCC) as part of an unspecific immunomodulatory treatment concept, seems to have ended with the introduction of targeted therapies. However, preliminary data from studies on treatment with checkpoint inhibitors (e. g. anti-PD-1 and anti-PD-L1) may point the way to second-generation immunotherapy. The rationale of such immunomodulatory treatment is to stop or interrupt the tumour from "escaping" the body's immune defence. Thompson et al. report that increased protein expression of PD-L1 (CD274/ B7-H1) in tumour cells and tumour-infiltrating immune cells (TILs; lymphocytes and histiocytes) is associated with unfavourable clinical pathological parameters as well as poor survival. In small pilot groups of mRCC patients it was found that increased PD-L1 protein expression in tumours and TILs may be correlated with the objective response to anti-PD-1 treatment. Sometimes, however, a very wide variety of response rates was observed, which raises the question if this can be explained by individual expression levels of PD-L1 (CD 274) or PD-1 (PDCD1).Recently published data from the Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) Network now provide a genome-wide data base that allows us to review or validate the molecular results obtained in clear cell renal cell carcinomas (ccRCC) to date.In this study, we analysed the TCGA KIRC mRNA expression data for PD-L1 and PD-1 for a possible association with clinical pathological parameters and the survival of 417 ccRCC patients.The mRNA expression of PD-L1 in primary nephrectomy specimens revealed no significant association with unfavourable clinical parameters. Interestingly, though, a positive correlation with patient survival was found (HR=0,59, p=0,006).These results, which partly contradict the concept applied to date, point out the necessity to ascertain the characteristics of PD-L1 and PD-1 expression at mRNA and protein level in an appropriately sized patient population and evaluate the clinical significance.
细胞因子时代，作为非特异性免疫调节治疗理念的一部分应用于转移性肾细胞癌（mRCC）患者，似乎随着靶向治疗的引入而结束。然而，关于检查点抑制剂（如抗PD - 1和抗PD - L1）治疗研究的初步数据可能为第二代免疫治疗指明方向。这种免疫调节治疗的基本原理是阻止或中断肿瘤“逃避”机体的免疫防御。汤普森等人报告称，肿瘤细胞和肿瘤浸润免疫细胞（TILs；淋巴细胞和组织细胞）中PD - L1（CD274 / B7 - H1）蛋白表达增加与不良临床病理参数以及较差的生存率相关。在mRCC患者的小型试验组中发现，肿瘤和TILs中PD - L1蛋白表达增加可能与抗PD - 1治疗的客观反应相关。然而，有时观察到的反应率差异很大，这就提出了一个问题，即这是否可以用PD - L1（CD 274）或PD - 1（PDCD1）的个体表达水平来解释。癌症基因组图谱（TCGA）肾透明细胞癌（KIRC）网络最近发表的数据现在提供了一个全基因组数据库，使我们能够回顾或验证迄今为止在透明细胞肾细胞癌（ccRCC）中获得的分子结果。在本研究中，我们分析了417例ccRCC患者的TCGA KIRC中PD - L1和PD - 1的mRNA表达数据，以探讨其与临床病理参数及生存情况的可能关联。原发性肾切除标本中PD - L1的mRNA表达与不良临床参数无显著关联。然而，有趣的是，发现其与患者生存率呈正相关（HR = 0.59，p = 0.006）。这些结果在一定程度上与迄今应用的概念相矛盾，指出有必要在适当规模的患者群体中确定mRNA和蛋白水平上PD - L1和PD - 1表达的特征，并评估其临床意义。
