PD-L1, B7-H3 and VISTA are highly expressed in gestational trophoblastic neoplasia
PD-L1, B7-H3 and VISTA are highly expressed in gestational trophoblastic neoplasia
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PD-L1、B7-H3 和 VISTA 在妊娠滋养细胞肿瘤中高表达
DOI：
10.1111/his.13882
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发表时间：
2019-09-01
期刊：
影响因子：
6.4
通讯作者：
Xiang, Yang
中科院分区：
文献类型：
--
作者：
Zong, Liju;Zhang, Ming;Xiang, Yang
目的 B7 家族检查点分子是癌症免疫疗法的潜在治疗靶点。然而，它们在人类妊娠滋养细胞肿瘤（GTN）中的表达状态仍然未知。我们研究了 B7 家族检查点蛋白 PD-L1、PD-L2、B7-H3、B7-H4、VISTA 和 B7-H6 在 GTN 中的表达谱及其临床意义。方法和结果 我们确定了 112 名 GTN 患者，其中 68 名绒毛膜癌、33 名胎盘部位滋养细胞肿瘤 (PSTT) 和 11 名上皮样滋养细胞肿瘤 (ETT)。使用抗 B7 家族抗体对全组织 GTN 切片进行免疫组织化学染色。使用正常人体组织和 20 种常见癌症的微阵列对 VISTA 表达进行免疫组织化学分析。 PD-L1和B7-H3在所有GTN肿瘤中高表达，而PD-L2在87.5%的样本中表达。 B7-H4 和 B7-H6 分别在 100% 和 98.2% 的样本中呈阴性。绒毛膜癌和 PSTT 中的 PD-L1、B7-H3 和 VISTA 水平显着高于 ETT。肿瘤细胞中的 B7 家族检查点表达与疾病分期、预后评分或患者结果（完全缓解与死亡）之间没有关联。 VISTA 蛋白在 98.2% 的 GTN 中广泛过表达，但其表达在其他癌症类型中有所不同，并且在除胎盘滋养层和脾淋巴细胞之外的正常成人和胎儿组织中呈阴性。结论 GTN 滋养层细胞以独立于临床结果的方式显示 PD-L1、B7-H3 和 VISTA 高表达。这些蛋白可能是治疗 GTN 时潜在的免疫治疗靶点。
Aims The B7 family check-point molecules are potential therapeutic targets in cancer immunotherapy. However, their expression status in human gestational trophoblastic neoplasia (GTN) remains unknown. We investigated the expression profiles of the B7 family check-point proteins PD-L1, PD-L2, B7-H3, B7-H4, VISTA and B7-H6 in GTN and their clinical significance. Methods and results We identified 112 patients with GTN, including 68 with choriocarcinoma, 33 with placental-site trophoblastic tumour (PSTT) and 11 with epithelioid trophoblastic tumour (ETT). Immunohistochemical staining was performed on whole-tissue GTN sections using anti-B7 family antibodies. VISTA expression was immunohistochemically analysed using microarrays of normal human tissues and of 20 common cancers. PD-L1 and B7-H3 were highly expressed in all GTN tumours, while PD-L2 was expressed in 87.5% of the samples. B7-H4 and B7-H6 were negative in 100% and 98.2% of the samples, respectively. PD-L1, B7-H3 and VISTA levels were significantly higher in choriocarcinomas and PSTTs than in ETTs. There was no association between B7 family check-point expression in tumour cells and disease stage, prognostic score or patient outcomes (complete remission versus death). VISTA protein was widely overexpressed in 98.2% of all the GTN, but its expression varied in other cancer types and was negative in normal adult and fetal tissues except placental trophoblasts and splenic lymphocytes. Conclusions The GTN trophoblast cells show high expression of PD-L1, B7-H3 and VISTA in a manner that is independent of clinical outcomes. These proteins may be potential immunotherapeutic targets when treating GTN.