PD-L1 Expression in Human Placentas and Gestational Trophoblastic Diseases.
PD-L1 Expression in Human Placentas and Gestational Trophoblastic Diseases.
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DOI：
10.1097/pgp.0000000000000305
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Shih IM
中科院分区：
文献类型：
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作者：
Veras E;Kurman RJ;Wang TL;Shih IM
程序性细胞死亡-1 （PD-1）与其配体（PD-L1）之间的相互作用是导致癌细胞免疫逃避的主要免疫检查点之一。由于人类滋养细胞表现出许多恶性细胞的特征，例如能够侵入包括血管在内的正常组织，并且显然不能被宿主免疫系统根除，因此我们进行了本研究，以确定在正常妊娠和妊娠滋养细胞疾病期间不同类型的滋养细胞中PD-L1是否上调。使用抗PD-L1特异性抗体的免疫组织化学表明，在早期和足月正常胎盘中，PD-L1在合胞滋养细胞中高度表达，而在绒毛膜叶和着床部位的中间滋养细胞中表达的程度要低得多。PD-L1免疫反应性在细胞滋养层细胞中检测不到。正常胎盘的这种染色模式在各种类型的妊娠滋养细胞疾病中都有重现。PD-L1在完全痣和绒毛膜癌中通过合体滋养细胞高度表达。中间滋养细胞肿瘤、胎盘部位滋养细胞肿瘤和上皮样滋养细胞肿瘤均表现出不同的PD-L1免疫反应性，但其强度低于绒毛膜癌的肿瘤合胞滋养细胞。此外，我们还观察到PD-1阳性淋巴细胞位于植入部位和滋养细胞肿瘤中。综上所述，本研究描述了滋养细胞通过上调合胞滋养细胞和中间滋养细胞中的PD-L1来产生耐受性胎母界面的新机制。滋养细胞肿瘤也可能利用PD-L1的表达来逃避宿主免疫反应，从而促进其生存。
One of the major immune checkpoints responsible for immune evasion in cancer cells is the interaction between programmed cell death-1 (PD-1) and its ligand (PD-L1). Since human trophoblastic cells display many of the features of malignant cells such as the ability to invade normal tissue including blood vessels and are apparently not eradicated by the host immune system, we undertook the present study to determine whether PD-L1 was upregulated in different types of trophoblastic cells during normal pregnancy and in gestational trophoblastic diseases. Immunohistochemistry using an anti-PD-L1 specific antibody demonstrated that in early and term normal placentas, PD-L1 was highly expressed in syncytiotrophoblast and to a much lower extent in intermediate trophoblastic cells located in the chorion laeve and implantation site. PD-L1 immunoreactivity was undetectable in cytotrophoblastic cells. This staining pattern in normal placenta was recapitulated in various types of gestational trophoblastic disease. PD-L1 was highly expressed by syncytiotrophoblast in complete moles and choriocarcinomas. The intermediate trophoblastic neoplasms, placental site trophoblastic tumors and epithelioid trophoblastic tumors, showed variable PD-L1 immunoreactivity but at a lower intensity than in the neoplastic syncytiotrophoblast in choriocarcinoma. In addition, we observed PD-1 positive lymphocytes located within the implantation site and in trophoblastic tumors. In summary, this study describes a novel mechanism for trophoblastic cells to create a tolerogenic feto-maternal interface by upregulating PD-L1 in syncytiotrophoblast and in intermediate trophoblast. Trophoblastic tumors may also use PD-L1 expression to evade the host immune response thereby promoting their survival.