PD-L1 Expression in Premalignant and Malignant Trophoblasts From Gestational Trophoblastic Diseases Is Ubiquitous and Independent of Clinical Outcomes

Bolze, Pierre‐Adrien; Patrier, Sophie; Massardier, Jérôme; Hajri, Touria; Abbas, Fatima; Schott, Anne-Marie; Allias, Fabienne; Devouassoux‐Shisheboran, Mojgan; Freyer, Gilles; Golfier, François; You, Benoît

doi:10.1097/igc.0000000000000892

Cited by 73 publications

(55 citation statements)

References 23 publications

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“…Consistent with previous studies, our results confirmed the ubiquitous and strong expression of PD‐L1 in GTN. Additionally, we found that PD‐L2 protein was positive in 87.5% of GTN samples and that it correlated significantly with PD‐L1.…”

Section: Discussionsupporting

confidence: 92%

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

et al. 2019

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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. Thymus (0/3) Colon (0/3) Sternum (0/2) Myocardium (0/5) Spleen (0/5) Lung (0/5) Aorta (0/3) Diaphragm (0/3) Skin (0/5) Kidney (0/4) Ovary (0/1) Hippocampus (0/4) Adrenal (0/5) Bladder (0/3) Stomach (0/5) Small intestine (0/4) Oesophagus (0/2) Testis (0/2) Pancreas (0/5) Liver (0/5) Brain (0/5) Adult organs (number positive/total cores) Oesophagus (0/8) Tongue (0/3) Thyroid (0/14) Small intestine (0/11) Spleen (2/2) Brain (0/6) Bladder (0/4) Skeletal muscle (0/7) Prostate (0/3) Skin (0/3) Colon (0/11) Myocardium (0/3) Lung (0/16) Trachea (0/3) Pancreas (0/8) Seminal vesicle (0/1) Appendix (0/5) Rectum (0/8) Breast (0/5) Uterine cervix (0/10) Testis (0/7) Aorta (0/3) Liver (0/8) Placenta (28/28) Larynx (0/3) Penis (0/5) Uterus (0/4) Stomach (0/14) Kidney (0/5) Cancer samples (number positive/total cores) Brain (0/6) Larynx (1/3) Stomach (0/6) Ureter (1/5) Rectum (0/5) Breast (0/5) Penis (3/5) Thyroid (1/10) Uterus (0/8) Ovary (2/6) Kidney (0/10) Pancreas (0/5) Prostate (0/6) Colon (0/5) Lung (0/7) Oesophagus (0/4) Liver (0/6) Testis (0/3) Bladder (0/6) Uterine cervix (2/8)

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Section: Discussionsupporting

confidence: 92%

“…Programmed cell death ligand 1 (PD‐L1) is expressed in both placental trophoblasts and GTN, suggesting that this protein is involved in maternal immune tolerance and tumour immune escape. PD‐L1 belongs to the B7 family of immunoregulatory molecules, and has been extensively studied in human malignancies.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…This immune checkpoint blockade therapy, justified by a strong expression of PD-L1 in GTN, was recently approved in Merkel cell carcinoma with an excellent tolerance profile. 18,19 Efficacy, toxicity, patients inconvenience, and treatment cost of these promising alternatives need to be prospectively compared.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Second-Line 5-Day Dactinomycin in Case of Methotrexate Failure for Gestational Trophoblastic Neoplasia

Prouvot

Golfier

Massardier

et al. 2018

Int J Gynecol Cancer

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Given a 75.7% complete response rate in methotrexate failed low-risk GTN patients treated with second-line dactinomycin and an overall survival rate of 100% after third-line treatment, the use of dactinomycin should be favored as second-line, regardless of human chorionic gonadotropin level at the time of dactinomycin initiation. However, an interval between the termination of the antecedent pregnancy and methotrexate initiation longer than 6 months should encourage considering alternative therapeutic strategies.

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“…[113][114][115] Programmed death ligand 1 (PD-L1) is strongly expressed by GTN. 116,117 Outcomes were recently reported for 4 patients with drug-resistant GTN who received pembrolizumab, including 2 with metastatic choriocarcinoma and 2 with metastatic PSTT or mixed PSTT/ETT. 118 All patients had tumors with high levels of PD-L1 expression.…”

Section: Salvage Chemotherapymentioning

confidence: 99%

Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology

Abu‐Rustum

Yashar

Bean

et al. 2019

Journal of the National Comprehensive Cancer Network

105

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Gestational trophoblastic neoplasia (GTN), a subset of gestational trophoblastic disease (GTD), occurs when tumors develop in the cells that would normally form the placenta during pregnancy. The NCCN Guidelines for Gestational Trophoblastic Neoplasia provides treatment recommendations for various types of GTD including hydatidiform mole, persistent post-molar GTN, low-risk GTN, high-risk GTN, and intermediate trophoblastic tumor.

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PD-L1 Expression in Premalignant and Malignant Trophoblasts From Gestational Trophoblastic Diseases Is Ubiquitous and Independent of Clinical Outcomes

Cited by 73 publications

References 23 publications

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

Efficacy and Safety of Second-Line 5-Day Dactinomycin in Case of Methotrexate Failure for Gestational Trophoblastic Neoplasia

Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology

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