REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1658681
This article is part of the Research TopicImmunological Aspects and Immunotherapy in Gynecologic CancersView all 18 articles
The Dual Nature of Immunotherapy in Female Reproductive Disorders: Immune Homeostasis and Clinical Challenges
Provisionally accepted
- Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing, China
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The female reproductive system (FRS) exhibits unique immunological characteristics, balancing defense against pathogens with tolerance to sperm and semi-allogeneic embryos. Key players include decidual natural killer (dNK) cells, immune checkpoint molecules (ICMs) and a complex immune microenvironment (IME).Dysregulation of these elements contributes to diseases like recurrent spontaneous abortion (RSA), endometriosis, primary ovarian insufficiency (POI), and infertility. Immunotherapy, particularly immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T-cell therapy, shows significant promise in treating gynecological malignancies (e.g., cervical, endometrial, ovarian cancers), especially in advanced/recurrent settings or with specific biomarkers like mismatch repair deficiency. However, challenges persist, including limited efficacy in microsatellite stable tumors, resistance mechanisms and significant immune-related adverse events (irAEs). Critically, emerging evidence indicates potential detrimental effects of immunotherapy (especially ICIs) on female reproductive function, including diminished ovarian reserve, impaired oocyte maturation, hormonal disruption, and possible infertility, mediated by inflammatory responses, gonadotoxicity, and disruption of immune tolerance. Management of female-specific toxicities requires personalized strategies, fertility assessment, and consideration of preservation techniques. Future directions emphasize the development of predictive biomarkers, optimization of combination therapies , and implementation of truly individualized treatment regimens that account for the unique FRS IME, sex hormone influences, and the imperative to preserve fertility. Addressing the reproductive toxicity of novel immunotherapies remains a critical unmet research need.
Keywords: immune checkpoint inhibitors, reproductive toxicity, gynecologic malignancies, Immune homeostasis, Fertility Preservation
Received: 03 Jul 2025; Accepted: 01 Sep 2025.
Copyright: © 2025 Abulajiang, He and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yue He, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing, China
Yumei Wu, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing, China
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