Immune Checkpoint Inhibitors: Sculpting the Landscape of Endometrial Cancer Treatment
- 1Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
Abstract
Background: Outcomes for advanced or recurrent endometrial cancer (EC) remain poor, with historically limited systemic options beyond platinum-based chemotherapy. EC is uniquely immunotherapy-amenable among solid tumors: it harbors the highest prevalence of mismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-H) status of any cancer, and its molecular classification into four major molecular subtypes defines a spectrum of tumor mutational burden, neoantigen load, and immune infiltration that predicts the response to checkpoint blockade. Current Landscape: Over the past several years, multiple programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have received regulatory approval in EC, spanning monotherapy in dMMR/MSI-H disease, combination with carboplatin–paclitaxel in the first-line advanced setting, and combination with anti-angiogenic therapy in biomarker-unselected recurrent disease, fundamentally altering the standard of care. Scope and Objectives: This narrative review synthesizes the molecular rationale for checkpoint inhibition in EC, including the biological basis of its molecular subtypes and their immune microenvironments, and provides a focused overview of the trial evidence supporting each major checkpoint inhibitor class, including PD-1 inhibitors, PD-L1 inhibitors, cytotoxic T-lymphocyte-associated protein 4 inhibitors, and emerging targets. We further review the landscape of ongoing trials addressing unresolved questions, including chemotherapy-free regimens in dMMR disease, maintenance intensification for mismatch repair-proficient (pMMR) disease, neoadjuvant and fertility-sparing approaches, and novel combinations. This review aims to provide a comprehensive, up-to-date synthesis of this rapidly evolving field and to identify challenges and opportunities that will shape the next phase of immunotherapy in EC.
Related
- Integration of Immune checkpoint inhibitors within the definitive radiotherapy-based treatment continuum for locally advanced mucosal head and neck squamous cell carcinoma: a scoping review protocol
- Successful Treatment of Synchronous Double Lung and Colon Cancers Using Immune Checkpoint Inhibitors
- Mechanisms of resistance to immune checkpoint inhibitors in renal cell carcinoma and novel treatment strategies
- Utilization of immune checkpoint inhibitors for the treatment of cancer in Scotland, 2018–2024: A national retrospective cohort study
- Comprehensive real-world utilization, treatment trajectories, and outcomes of immune checkpoint inhibitors across cancer types: the multicenter FAIR-ICI cohort
BibTeX
@article{huang2026immune,
title = {{Immune Checkpoint Inhibitors: Sculpting the Landscape of Endometrial Cancer Treatment}},
author = {Allan B. Huang and Lakeisha Mulugeta-Gordon and Dimitrios Nasioudis and Janos L. Tanyi},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18213431},
url = {https://www.mdpi.com/2072-6694/18/21/3431},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Immune Checkpoint Inhibitors: Sculpting the Landscape of Endometrial Cancer Treatment
AU - Allan B. Huang
AU - Lakeisha Mulugeta-Gordon
AU - Dimitrios Nasioudis
AU - Janos L. Tanyi
PY - 2026
DA - 2026/10/23
JO - Cancers
DO - 10.3390/cancers18213431
UR - https://www.mdpi.com/2072-6694/18/21/3431
AB - Background: Outcomes for advanced or recurrent endometrial cancer (EC) remain poor, with historically limited systemic options beyond platinum-based chemotherapy. EC is uniquely immunotherapy-amenable among solid tumors: it harbors the highest prevalence of mismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-H) status of any cancer, and its molecular classification into four major molecular subtypes defines a spectrum of tumor mutational burden, neoantigen load, and immune infiltration that predicts the response to checkpoint blockade. Current Landscape: Over the past several years, multiple programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have received regulatory approval in EC, spanning monotherapy in dMMR/MSI-H disease, combination with carboplatin–paclitaxel in the first-line advanced setting, and combination with anti-angiogenic therapy in biomarker-unselected recurrent disease, fundamentally altering the standard of care. Scope and Objectives: This narrative review synthesizes the molecular rationale for checkpoint inhibition in EC, including the biological basis of its molecular subtypes and their immune microenvironments, and provides a focused overview of the trial evidence supporting each major checkpoint inhibitor class, including PD-1 inhibitors, PD-L1 inhibitors, cytotoxic T-lymphocyte-associated protein 4 inhibitors, and emerging targets. We further review the landscape of ongoing trials addressing unresolved questions, including chemotherapy-free regimens in dMMR disease, maintenance intensification for mismatch repair-proficient (pMMR) disease, neoadjuvant and fertility-sparing approaches, and novel combinations. This review aims to provide a comprehensive, up-to-date synthesis of this rapidly evolving field and to identify challenges and opportunities that will shape the next phase of immunotherapy in EC.
SN - 2072-6694
ER -