PD‐L1, B7‐H3 and VISTA are highly expressed in gestational trophoblastic neoplasia

• Published in: Histopathology 2019-09, Vol.75 (3), p.421-430
• Main Authors: Zong, Liju, Zhang, Ming, Wang, Wenze, Wan, Xirun, Yang, Junjun, Xiang, Yang
• Format: Article
• Language: English
• Subjects: Adult; B7 antigen; B7 Antigens - biosynthesis; B7 family checkpoints; B7-H1 Antigen - biosynthesis; B7‐H3; Biomarkers, Tumor - analysis; Cancer immunotherapy; Female; Fetuses; Gestational Trophoblastic Disease - metabolism; Gestational Trophoblastic Disease - pathology; gestational trophoblastic neoplasia; Humans; Immunotherapy; Lymphocytes; Middle Aged; Patients; PD-L1 protein; PD‐L1; Placenta; Pregnancy; Remission; Spleen; Therapeutic applications; Trophoblasts; Tumors; VISTA; Young Adult
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.13882

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.