REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicImmunological Aspects and Immunotherapy in Gynecologic CancersView all 27 articles
Immunotherapy in Endometrial Cancer: Mechanisms, Clinical Evidence, and Future Directions
Provisionally accepted
- 1Department of Obstetrics and Gynecology, Longquan People's Hospital, Lishui, China
- 2Innovative Regenerative Medicine, Graduate School of Medicine, Kansai Medical University, Hirakata city, Japan
- 3Department of Gynecology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- 4Sixth Medical Center of PLA General Hospital, Beijing, China
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Endometrial cancer (EC) treatment has been revolutionized by the integration of immunotherapy, particularly for molecularly defined subsets of patients. The classification of EC into DNA polymerase epsilon-mutated (POLE-mutant), mismatch repair-deficient (dMMR), p53-abnormal, and no specific molecular profile (NSMP) subtypes provides a critical framework for predicting response to immune checkpoint blockade. dMMR and POLE-mutant tumors, with their hypermutated and immunogenic phenotypes, demonstrate exceptional sensitivity to Programmed Death-1(PD-1) inhibitors such as pembrolizumab and dostarlimab in clinical trials. In contrast, overcoming the immunoresistant nature of NSMP and p53-abnormal EC requires innovative combinations, exemplified by the success of pembrolizumab plus the multitargeted tyrosine kinase inhibitor lenvatinib. Recent practice-changing clinical trials have further established combination strategies incorporating PD-1 blockade with chemotherapy as a new first-line standard for advanced disease, marking a paradigm shift in the management of advanced EC. This review synthesizes the mechanistic basis for these approaches, the compelling clinical evidence supporting approved therapies, and the frontier of investigational strategies, including cellular therapies, novel immune checkpoints, and rational combination regimens—aimed at expanding the benefit of immunotherapy to a broader range of patients with EC.
Keywords: endometrial cancer, Immunotherapy, immune checkpoint inhibitors, Molecular classification, MMR-deficiency, PD-1, Pembrolizumab, Dostarlimab
Received: 01 Sep 2025; Accepted: 17 Dec 2025.
Copyright: © 2025 Lian, Zhang, Li and Wang. 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:
Tianye Li
Aiming Wang
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