Immunotherapy in gestational trophoblastic neoplasia: advances and future directions

Gestational trophoblastic neoplasia (GTN) is a rare but aggressive malignancy that follows normal or aberrant pregnancies. Until the advent of immunotherapy in 2017, surgery and chemotherapy were the standard treatment modalities, with chemotherapy remaining the cornerstone. However, chemoresistance...

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Main Authors: Jing Zeng, Jing Zhang, Jianzhang Wang, Lian Xu, Cheng Wang, Rutie Yin
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1544585/full
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author Jing Zeng
Jing Zeng
Jing Zhang
Jing Zhang
Jianzhang Wang
Lian Xu
Lian Xu
Cheng Wang
Cheng Wang
Rutie Yin
Rutie Yin
author_facet Jing Zeng
Jing Zeng
Jing Zhang
Jing Zhang
Jianzhang Wang
Lian Xu
Lian Xu
Cheng Wang
Cheng Wang
Rutie Yin
Rutie Yin
author_sort Jing Zeng
collection DOAJ
description Gestational trophoblastic neoplasia (GTN) is a rare but aggressive malignancy that follows normal or aberrant pregnancies. Until the advent of immunotherapy in 2017, surgery and chemotherapy were the standard treatment modalities, with chemotherapy remaining the cornerstone. However, chemoresistance and high-risk disease present significant challenges in managing GTN. Recent advancements in immunotherapy, particularly immune checkpoint inhibitors (ICIs), have offered new hope for managing these difficult cases. This review provides the comprehensive overview of the mechanisms underlying ICIs in GTN, and explores the potential synergy of combining ICIs with targeted therapies, such as vascular endothelial growth factor and epidermal growth factor receptor inhibitors. We also provide an overview of the latest evidence on the use of ICIs in treating GTN, focusing on their effectiveness in both low- and high-risk cases, as well as in chemorefractory settings. In addition, we discuss ongoing clinical trials, immune-related adverse events associated with ICIs, biomarker-driven approaches, immunosuppressive tumor microenvironments, and the challenges posed with ICIs resistance. The review also explores future directions, including the integration of ICIs into standard regimens, the potential for personalized treatment based on tumor biology, and the importance of fertility preservation in young patients with GTN. In conclusion, while challenges remain, immunotherapy represents a promising frontier in GTN treatment, with the potential to improve outcomes and provide a more personalized approach to care
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spelling doaj-art-ca9dcc2779604e7daf25cc252d68ab1e2025-08-20T02:09:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15445851544585Immunotherapy in gestational trophoblastic neoplasia: advances and future directionsJing Zeng0Jing Zeng1Jing Zhang2Jing Zhang3Jianzhang Wang4Lian Xu5Lian Xu6Cheng Wang7Cheng Wang8Rutie Yin9Rutie Yin10Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, ChinaKey Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, Sichuan, ChinaKey Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, Sichuan, ChinaJoint Laboratory of Reproductive Medicine (SCU-CUHK), West China Second University Hospital, Sichuan University, Chengdu, Sichuan, ChinaWest China School of Medicine, Sichuan University, Chengdu, Sichuan, ChinaKey Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, Sichuan, ChinaDepartment of Pathology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, ChinaKey Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, Sichuan, ChinaDepartment of Pathology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, ChinaKey Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, Sichuan, ChinaGestational trophoblastic neoplasia (GTN) is a rare but aggressive malignancy that follows normal or aberrant pregnancies. Until the advent of immunotherapy in 2017, surgery and chemotherapy were the standard treatment modalities, with chemotherapy remaining the cornerstone. However, chemoresistance and high-risk disease present significant challenges in managing GTN. Recent advancements in immunotherapy, particularly immune checkpoint inhibitors (ICIs), have offered new hope for managing these difficult cases. This review provides the comprehensive overview of the mechanisms underlying ICIs in GTN, and explores the potential synergy of combining ICIs with targeted therapies, such as vascular endothelial growth factor and epidermal growth factor receptor inhibitors. We also provide an overview of the latest evidence on the use of ICIs in treating GTN, focusing on their effectiveness in both low- and high-risk cases, as well as in chemorefractory settings. In addition, we discuss ongoing clinical trials, immune-related adverse events associated with ICIs, biomarker-driven approaches, immunosuppressive tumor microenvironments, and the challenges posed with ICIs resistance. The review also explores future directions, including the integration of ICIs into standard regimens, the potential for personalized treatment based on tumor biology, and the importance of fertility preservation in young patients with GTN. In conclusion, while challenges remain, immunotherapy represents a promising frontier in GTN treatment, with the potential to improve outcomes and provide a more personalized approach to carehttps://www.frontiersin.org/articles/10.3389/fimmu.2025.1544585/fullgestational trophoblastic neoplasiaimmune checkpoint inhibitorschemoresistanceclinical trialsfertility preservationimmune-related adverse events
spellingShingle Jing Zeng
Jing Zeng
Jing Zhang
Jing Zhang
Jianzhang Wang
Lian Xu
Lian Xu
Cheng Wang
Cheng Wang
Rutie Yin
Rutie Yin
Immunotherapy in gestational trophoblastic neoplasia: advances and future directions
Frontiers in Immunology
gestational trophoblastic neoplasia
immune checkpoint inhibitors
chemoresistance
clinical trials
fertility preservation
immune-related adverse events
title Immunotherapy in gestational trophoblastic neoplasia: advances and future directions
title_full Immunotherapy in gestational trophoblastic neoplasia: advances and future directions
title_fullStr Immunotherapy in gestational trophoblastic neoplasia: advances and future directions
title_full_unstemmed Immunotherapy in gestational trophoblastic neoplasia: advances and future directions
title_short Immunotherapy in gestational trophoblastic neoplasia: advances and future directions
title_sort immunotherapy in gestational trophoblastic neoplasia advances and future directions
topic gestational trophoblastic neoplasia
immune checkpoint inhibitors
chemoresistance
clinical trials
fertility preservation
immune-related adverse events
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1544585/full
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AT jianzhangwang immunotherapyingestationaltrophoblasticneoplasiaadvancesandfuturedirections
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