Analysis of PD-L1 expression in trophoblastic tissues and tumors
Analysis of PD-L1 expression in trophoblastic tissues and tumors
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DOI：
10.1016/j.humpath.2018.10.001
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发表时间：
2019-02-01
期刊：
影响因子：
3.3
通讯作者：
Lu, Yan
中科院分区：
文献类型：
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作者：
Lu, Bingjian;Teng, Xiaodong;Lu, Yan
免疫检查点蛋白，程序性死亡受体1（PD-1）和程序性死亡配体1（PD-L1），对于维持胎儿母体免疫耐受和癌症免疫逃逸至关重要。在这项研究中，我们进行了一个全面的免疫组化研究PD-L1的表达在一个大型队列的滋养层组织和肿瘤。我们发现，正常绒毛和葡萄胎显示出滋养层中的不均匀PD-L1染色（合体滋养层中强，中间滋养层中中等，细胞滋养层中弱/阴性）。11个夸张的胎盘部位（100%）显示出不同的PD-L1染色，而19个胎盘部位结节/斑块中有7个（36.8%）PD-L1呈弱阳性（P < .001）。所有妊娠绒毛膜癌（CC; n = 63）、上皮样滋养细胞肿瘤（n = 12）和胎盘部位滋养细胞肿瘤（n = 41）均为PD-L1阳性，大多数显示强染色。然而，PD-L1在上皮样滋养细胞肿瘤中的表达低于胎盘部位滋养细胞肿瘤和CC（P = .004）。3个推测为生殖细胞来源的纯CC、13个混合生殖细胞肿瘤中的CC成分和4个胃/直肠CC也对PD-L1呈阳性，并具有广泛的染色。背景非滋养层组织，如子宫内膜腺体、鳞状细胞和腺癌，均为PD-L1阴性。Western blot分析显示PD-L1在3种滋养层细胞系中均有表达。我们得出结论，PD-L1是滋养层细胞和相关肿瘤的敏感但非特异性标志物。频繁的强PD-L1表达表明，免疫检查点阻断可能是治疗滋养细胞肿瘤的一种有前途的方法，值得进一步研究。(C)2018爱思唯尔公司All rights reserved.
The immune checkpoint proteins, programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1), are crucial for maintaining fetomatemal immune tolerance and immune escape in cancers. In this study, we performed a comprehensive immunohistochemical study of PD-L1 expression in a large cohort of trophoblastic tissues and tumors. We found that normal villi and hydatidiform moles showed a heterogeneous PD-L1 staining among trophoblast (strong in syncytiotrophoblast, moderate in intermediate trophoblast, and weak/negative in cytotrophoblast). Eleven exaggerated placental sites (100%) showed variable PD-L1 staining, whereas 7 (36.8%) of 19 placental site nodules/plaques were weakly positive for PD-L1 (P < .001). All gestational choriocarcinomas (CCs; n = 63), epithelioid trophoblastic tumors (n = 12), and placental site trophoblastic tumors (n = 41) were PD-L1 positive, with most showing strong staining. However, PD-L1 expression was lower in epithelioid trophoblastic tumors compared with placental site trophoblastic tumors and CCs (P = .004). Three presumably germ cell derived pure CCs, the CC elements in 13 mixed germ cell tumors, and 4 gastric/rectal CCs were also positive for PD-L1, with widespread staining. The background nontrophoblastic tissues, such as endometrial glands, squamous cells, and adenocarcinomas, were PD-L1 negative. Western blot analysis showed that PD-L1 was expressed in all 3 trophoblastic cell lines. We conclude that PD-L1 is a sensitive but nonspecific marker for trophoblast and related tumors. The frequent strong PD-L1 expression suggests that immune checkpoint blockade could be a promising approach in treating trophoblastic tumors that merits further investigation. (C) 2018 Elsevier Inc. All rights reserved.