Chinese Medical E-ournals Database

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2026, Vol. 22 ›› Issue (01): 1 -6. doi: 10.3877/cma.j.issn.1673-5250.2026.01.001

Expert Editorial

Current research status of immunotherapy for gestational trophoblastic neoplasia

Shunyao Meng1, Jing Zeng2, Rutie Yin2,()   

  1. 1Department of Obstetrics and Gynecology, Meishan Women and Children′s Hospital, Alliance Hospital of West China Second University Hospital, Sichuan University, Meishan 620000, Sichuan Province, China
    2Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Disseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2025-10-28 Revised:2025-11-30 Published:2026-02-01
  • Corresponding author: Rutie Yin
  • Supported by:
    Key Research Project of Science and Technology Department of Sichuan Province: Key Factors Affecting the Diagnosis and Treatment of Major Diseases in Obstetrics and Gynecology(2019YFS0532); Horizontal Science and Technology Project of Sichuan University: Real-World Study on Targeted Immunotherapy for Gynecological Malignant Tumors(23H1223)

Immunotherapy has emerged and gradually gained attention and recognition in the comprehensive management of gestational trophoblastic neoplasia (GTN). In recent years, with continuous exploration of the pathogenesis of GTN, certain progress has been made in the field of GTN immunotherapy. The combined application of immunotherapy with chemotherapeutic drugs and novel targeted drugs has provided new treatment strategies and hopes for cure of patients with drug-resistant and refractory GTN. This article reviews the latest progress in immunotherapy for patients with GTN, aiming to provide more references and assistance for clinicians.

图1 FIGO推荐的对GTN患者的标准诊疗流程图注:FIGO为国际妇产科联盟。GTN为妊娠滋养细胞肿瘤。hCG为绒膜促性腺激素。EMA为依托泊苷+甲氨蝶呤+放线菌素D,CO为环磷酰胺+长春新碱,EP为依托泊苷+顺铂,TP为紫杉醇+顺铂,TE为紫杉醇+依托泊苷,VIP为依托泊苷+异环磷酰胺+顺铂,ICE为异环磷酰胺+卡铂+依托泊苷,BEP为博来霉素+依托泊苷+顺铂,FAEV为氟尿嘧啶+放线菌素D+依托泊苷+长春新碱
图2 GTN中PD-1/PD-L1阻断的发病机制图注:GTN为妊娠滋养细胞肿瘤。PD-1/PD-L1是程序性死亡受体1/程序性死亡受体配体1。B7配体家族、CD28受体家族均属于免疫球蛋白超家族
[1]
Ngan HYS, Seckl MJ, Berkowitz RS, et al. Diagnosis and management of gestational trophoblastic disease: 2025 update[J].Int J Gynaecol Obstet, 2025, 171(Suppl 1): 78-86. DOI: 10.1002/ijgo.70275.
[2]
Braga A, Mora P, de Melo AC, et al. Challenges in the diagnosis and treatment of gestational trophoblastic neoplasia worldwide[J].World J Clin Oncol, 2019, 10(2): 28-37. DOI: 10.5306/wjco.v10.i2.28.
[3]
李克敏,尹如铁. 高危妊娠滋养细胞肿瘤的治疗[J]. 中国实用妇科与产科杂志2022, 38(7): 691-693. DOI: 10.19538/j.fk2022070106.
[4]
Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice[J]. Nat Rev Immunol, 2020, 20(11): 651-668. DOI: 10.1038/s41577-020-0306-5.
[5]
McNally L, Wu S, Hodges K, et al. Molecular profiling of gestational trophoblastic neoplasia: identifying therapeutic targets[J]. Gynecol Oncol, 2024, 184(1): 111-116. DOI: 10.1016/j.ygyno.2024.01.033.
[6]
Htanaka K, Higashi M, Fujibayashi M, et al. A case of complete hydatidiform mole in a perimenopausal woman with diagnostic usefulness of p57kip2 immunohistochemistry and HER2 fluorescent in situ hybridization[J]. Pathol Res Pract, 2012, 208(1): 118-120. DOI: 10.1016/j.prp.2011.11.005.
[7]
Lala PK, Nandi P, Hadi A, et al. A crossroad between placental and tumor biology: what have we learnt[J].Placenta, 2021, 116(1): 12-30. DOI: 10.1016/j.placenta.2021.03.003.
[8]
Veras E, Kurman RJ, Wang TL, et al. PD-L1 expression in human placentas and gestational trophoblastic diseases[J].Int J Gynecol Pathol, 2017, 36(2): 146-153. DOI: 10.1097/PGP.0000000000000305.
[9]
Choi MC, Oh J, Lee C. Effective anti-programmed cell death 1 treatment for chemoresistant gestational trophoblastic neoplasia[J].Eur J Cancer, 2019, 121(1): 94-97. DOI: 10.1016/j.ejca.2019.08.024.
[10]
Zeng J, Zhang J, Wang J, et al. Immunotherapy in gestational trophoblastic neoplasia: advances and future directions[J].Front Immunol, 2025, 16: 1544585. DOI: 10.3389/fimmu.2025.1544585.
[11]
中国抗癌协会肿瘤内分泌专业委员会. 妇科恶性肿瘤免疫治疗中国专家共识(2023年版)[J]. 中国癌症杂志2023, 33(10): 954-968. DOI: 10.19401/j.cnki.1007-3639.2023.10.008.
[12]
Zong L, Zhang M, Wang W, et al. PD-L1, B7-H3 and VISTA are highly expressed in gestational trophoblastic neoplasia[J/OL]. Histopathology, 2019, 75(3): 421-430. DOI: 10.1111/his.13882.
[13]
You B, Bolze PA, Lotz JP, et al. Avelumab in patients with gestational trophoblastic tumors with resistance to single-agent chemotherapy: cohort A of the TROPHIMMUN phase Ⅱ trial[J/OL]. J Clin Oncol, 2020, 38(27): 3129-3137. DOI: 10.1200/jco.20.008038.
[14]
You B, Lotz JP, Descargues P, et al. 7110 Avelumab + methotrexate to eradicate low-risk gestational trophoblastic tumors in first-line setting: TROPHAMET phase Ⅰ/Ⅱ trial[J]. Ann Oncol, 2024, 35(Supp 2): S545. DOI: 10.1016/j.annonc.2024.08.772.
[15]
Wang W, Yang J, Xiang Y. Advancing immunotherapy in gestational trophoblastic neoplasia: current progress and future directions[J]. Gynecol Obstet Clin Med, 2025, 5: e000194. DOI:10.1136/gocm-2024-000194.
[16]
You B, Bolze P, Lotz J, et al. 273 Avelumab in patients with gestational trophoblastic tumors resistant to polychemotherapy: efficacy outcomes of cohort B of TROPHIMMUN phase Ⅱ trial[J]. Trophoblastic Diseases, 2021, 31(Supp 1): A344.2-A344. DOI: 10.1136/ijgc-2021-esgo.608.
[17]
Cheng H, Yang J, Zhao J, et al. 177 Camrelizumab combined with apatinib for refractory gestational trophoblastic neoplasia: a phase 2, single-arm, prospective study[J]. Int J Gynecol Cancer, 2020, 30(Suppl 3): A76. DOI: 10.1136/IJGC-2020-IGCS.154.
[18]
Wang X, Cang W, Liu X, et al. Anti-PD-1 therapy plus chemotherapy versus anti-PD-1 therapy alone in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia: a multicenter, retrospective study[J]. EClinicalMed, 2023, 59: 101974. DOI: 10.1016/j.eclinm.2023.101974.
[19]
Porte A, Barcelon JM, Budker RL, et al. Treatment of metastatic placental site trophoblastic tumor with surgery, chemotherapy, immunotherapy and coil embolization of multiple pulmonary arteriovenous fistulate[J].Gynecol Oncol Rep, 2021, 36: 100782. DOI: 10.1016/j.gore.2021.100782.
[20]
Ghorani E, Kaur B, Fisher RA, et al. Pembrolizumab is effective for drug-resistant gestational trophoblastic neoplasia[J].Lancet, 2017, 390(10110): 2343-2345. DOI: 10.1016/S0140-6736(17)32894-5.
[21]
Bolze PA, Patrier S, Massardier J, et al. PD-L1 expression in premalignant and malignant trophoblasts from gestational trophoblastic diseases is ubiquitous and independent of clinical outcomes[J].Int J Gynecol Cancer, 2017, 27(3): 554-561. DOI: 10.1097/IGC.0000000000000892.
[22]
Pisani D, Calleja-Agius J, Di Fiore R, et al. Epithelioid trophoblastic tumour: a case with genetic linkage to a child born over seventeen years prior, successfully treated with surgery and pembrolizumab[J].Curr Oncol, 2021, 28(6): 5346-5355. DOI: 10.3390/curroncol28060446.
[23]
Winship AL, Alesi LR, Sant S, et al. Checkpoint inhibitor immunotherapy diminishes oocyte number and quality in mice[J]. Nat Cancer, 2022, 3(1): 1113. DOI: 10.1038/s43018-022-00413-x.
[24]
Garutti M, Lambertini M, Puglisi F. Checkpoint inhibitors, fertility, pregnancy, and sexual life: a systematic review[J]. ESMO Open, 2021, 6: 100276. DOI: 10.1016/j.esmoop.2021.100276.
[25]
Özdemir BC. Immune checkpoint inhibitor-related hypogonadism and infertility: a neglected issue in immuno-oncology[J]. J ImmunoTherapy Cancer, 2021, 9: e002220. DOI: 10.1136/jitc-2020-002220.
[26]
Chen Z, Huang J, Kwak-Kim J, et al. Immune checkpoint inhibitors and reproductive failures[J].J Reprod Immunol, 2023, 156: 103799. DOI: 10.1016/j.jri.2023.103799.
[27]
Johnson DB, Nebhan CA, Moslehi JJ, et al. Immune-checkpoint inhibitors: long-term implications of toxicity[J].Nat Rev Clin Oncol, 2022, 19(4): 254-267. DOI: 10.1038/s41571-022-00600-w.
[28]
Borgers JSW, Heimovaara JH, Cardonick E, et al. Immunotherapy for cancer treatment during pregnancy[J].Lancet Oncol, 2021, 22(12): e550-e561. DOI: 10.1016/S1470-2045(21)00525-8.
[29]
Mehta A, Kim KB, Minor DR. Case report of a pregnancy during ipilimumab therapy[J]. J Glob Oncol, 2018, 4: 1-3. DOI: 10.1200/JGO.17.00019.
[30]
Menzer C, Beedgen B, Rom J, et al. Immunotherapy with ipilimumab plus nivolumab in a stage IV melanoma patient during pregnancy[J].Eur J Cancer, 2018104:239-242. DOI:10.1016/j.ejca.2018.09.008.
[31]
Xu W, Moor RJ, Walpole ET, et al. Pregnancy with successful foetal and maternal outcome in a melanoma patient treated with nivolumab in the first trimester: case report and review of the literature[J].Melanoma Res, 2019, 29(3): 333-337. DOI: 10.1097/CMR.0000000000000586.
[32]
Bucheit AD, Hardy JT, Szender JB, et al. Conception and viable twin pregnancy in a patient with metastatic melanoma while treated with CTLA-4 and PD-1 checkpoint inhibition[J].Melanoma Res, 2020, 30(4): 423-425. DOI: 10.1097/CMR.0000000000000657.
[33]
Burotto M, Gormaz JG, Samtani S, et al. Viable pregnancy in a patient with metastatic melanoma treated with double checkpoint immunotherapy[J].Semin Oncol, 2018, 45(3): 164-169. DOI: 10.1053/j.seminoncol.2018.03.003.
[34]
Polnaszek B, Mullen M, Bligard K, et al. Term pregnancy after complete response of placental site trophoblastic tumor to immunotherapy[J].Obstet Gynecol, 2021, 138(1): 115-118. DOI: 10.1097/AOG.0000000000004434.
[35]
Harrold EC, Ogle M, O′Brien E, et al. Fertility outcomes post immune checkpoint inhibitor exposure[J].Cancer Cell, 2024, 42(11): 1808-1810. DOI: 10.1016/j.ccell.2024.10.005.
[1] Hongyu Jiang, Jialuo Liang, Lin Ma, Yongqiang Deng, Xinghan Li. Current advances in biomarkers associated with immunotherapy in oral and oropharyngeal squamous cell carcinoma[J]. Chinese Journal of Stomatological Research(Electronic Edition), 2026, 20(02): 136-148.
[2] Jianyong Liu, Yi Jiang. Application of immune checkpoint inhibitors neoadjuvant therapy in liver transplantation for hepatocellular carcinoma[J]. Chinese Archives of General Surgery(Electronic Edition), 2026, 20(02): 127-132.
[3] Junfeng Zhang, Yue Niu, Peng Chen. Real-world challenges and future directions of neoadjuvant and adjuvant strategies in locally advanced renal cell carcinoma[J]. Chinese Journal of Endourology(Electronic Edition), 2026, 20(03): 248-254.
[4] Wei Qiao, Qianxin Zhou, Yue Su, Yuan Ma, Sha Zhao. Dynamic immunogenicity analysis of Pneumocystis jirovecii infection prediction in patients with advanced non-small cell lung cancer after immunotherapy[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2026, 19(02): 181-188.
[5] Yanan Li, Xianghua Huang. Application of vaginal endoscopy in the diagnosis and treatment of female genital tract congenital anomalies[J]. Chinese Journal of Laparoscopic Surgery(Electronic Edition), 2026, 19(02): 77-82.
[6] Guineng Zeng, Penghui Yang, Rong Liu. Antitumor activity and immune activation effects of recombinant oncolytic influenza virus expressing IL-21 in pancreatic cancer[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2026, 16(03): 129-139.
[7] Linsen Ye, Yang Yang. Challenges and explorations of advanced liver cancer treatment: review and prospect[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(03): 290-298.
[8] Zheng Zhou, Shuai Hu, Maoyun Xie, Xiyan Zheng, Ting Liu, Zhiqun Lin, Xianqing Chen, Fei Du, Xianjie Shi. Research progress in perioperative adjuvant therapy for resectable hepatocellular carcinoma[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(03): 317-325.
[9] Shengxiong Jia, Yan Xu, Xiaojun He, Kai Tan, Xilin Du. Regulation of CD47-SIRPα axis and CD47 targeted therapy: a new strategy to resolve drug resistance of immunotherapy for pancreatic cancer[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(03): 337-345.
[10] Sijie Huang, Huiyong Zhang, Xiaohui Guo, Chengrun Xu. Prognostic value of systemic inflammatory response index in patients with advanced liver cancer after TACE combined with targeted immunotherapy[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(03): 355-361.
[11] Yongqing Ye, Shuaimei Luo, Shunqian Wen, Junpeng Chen, Xianhua Zhang, Liyun Huang, Qijun Lao, Qing Wu. Progress in targeted immunotherapy for intermediate-advanced hepatocellular carcinoma[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(03): 413-419.
[12] Wei Xie, Xiaofeng Zhang, Feng Shen. Eepidemiological characteristics, mechanism, prevention and treatment strategies of immune-related adverse events from tumor immunotherapy[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(02): 146-151.
[13] Chen Wang, Fang Xu, Fang Zhou, Jin Liu, Fang Sheng. Effect of fatty liver disease on clinical efficacy and prognosis of systemic treatment for advanced ICC[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(02): 226-233.
[14] Jing Zhao, Danling He, Shengjie Hong, Guangquan Zhang, Hanxi He. Prevention and treatment of immune-related skin complications from targeted therapy and immunotherapy for hepatocellular carcinoma[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(02): 266-270.
[15] Xiumei Chen, Manying Xie, Sijuan Chen, Xuhui Zhong, Qiao Pan, Lijuan Wen, Expert Consensus Writing Group. Expert consensus on nursing management of immune-related adverse events in patients with advanced non-small cell lung cancer[J]. Chinese Journal of Clinicians(Electronic Edition), 2026, 20(02): 77-89.
Viewed
Full text


Abstract