Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors
Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors
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DOI：
10.1093/annonc/mdv574
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发表时间：
2016-02-01
影响因子：
50.5
通讯作者：
Babal, P.
中科院分区：
文献类型：
--
作者：
Cierna, Z.;Mego, M.;Babal, P.
背景资料：睾丸生殖细胞肿瘤（TGCT）属于最敏感的实体瘤;然而，一小部分患者无法通过基于顺铂的化疗治愈。PD-1/PD-L1通路抑制剂代表了一类新的有前途的抗癌治疗药物。本研究的目的是评估PD-1和PD-L1在TGCTs.Patients和方法中的表达和预后价值：140例TGCTs患者（131例原发性睾丸肿瘤和9例性腺外GCTs）的手术标本被纳入翻译研究。采用免疫组化方法检测PD-1和PD-L1在肿瘤组织中的表达，采用QS评分法进行评分，并与正常睾丸组织中的表达进行比较，并与临床病理特征和临床结局进行相关性分析。GCT均未显示PD-1蛋白，尽管PD-L1在GCT中的表达显著高于正常睾丸组织（平均QS = 5.29比0.32，P < 0.0001）。绒毛膜癌表现出最高水平的PD-L1，而胚胎癌、畸胎瘤、卵黄囊瘤和卵巢癌的阳性率降低。PD-L1表达与不良预后特征相关，包括≥ 3个转移部位、血清肿瘤标志物升高和/或非肺内脏转移。PD-L1低表达患者的无进展生存期[风险比（HR）= 0.40，95%置信区间（CI）0.16-1.01，P = 0.008]和总生存期显著更好（HR = 0.43，95%CI 0.15-1.23，P = 0.040）。结论：在这项翻译研究中，我们首次显示了TGCT中PD-L1表达的预后价值，我们的数据表明PD-1/PD-L1通路可能是TGCT的新治疗靶点。
Background: Testicular germ cell tumors (TGCTs) belong to the most chemosensitive solid tumors; however, a small proportion of patients fail to be cured with cisplatin-based chemotherapy. Inhibitors of PD-1/PD-L1 pathways represent a new class of promising drugs in anticancer therapy. The aim of this study was to evaluate expression and prognostic value of PD-1 and PD-L1 in TGCTs.Patients and methods: Surgical specimens from 140 patients with TGCTs (131 with primary testicular tumor and 9 with extragonadal GCTs) were included into the translational study. PD-1 and PD-L1 expression was detected in the tumor tissue by immunohistochemistry usingmonoclonal antibodies, scored by the multiplicative quickscore (QS) method, compared with their expression in normal testicular tissue and correlated with clinicopathological characteristics and clinical outcome.Results: None of the GCTs exhibited PD-1 protein, although expression of PD-L1 was significantly higher in GCTs in comparison with normal testicular tissue (mean QS = 5.29 versus 0.32, P < 0.0001). Choriocarcinomas exhibit the highest level of PD-L1 with decreasing positivity in embryonal carcinoma, teratoma, yolk sac tumor and seminoma. PD-L1 expression was associated with poor prognostic features, including = 3 metastatic sites, increased serum tumor markers and/or non-pulmonary visceral metastases. Patients with low PD-L1 expression had significantly better progression-free survival [hazard ratio (HR) = 0.40, 95% confidence interval (CI) 0.16-1.01, P = 0.008] and overall survival (HR = 0.43, 95% CI 0.15-1.23, P = 0.040) compared with patients with high PD-L1 expression.Conclusions: In this translational study, we showed, for the first time, the prognostic value of PD-L1 expression in TGCTs and our data imply that the PD-1/PD-L1 pathway could be a novel therapeutic target in TGCTs.